I've included both the Manga synopsis and the Series Synopsis as a comparison of the two. Because As we all know. Anime tends to change when it gets overseas and on the big screen.

1. The Beginning
The two versions of the series begin differently, whether you want to count the "pilot" chapter of the manga or the first one of volume one as the beginning. The first three episodes have no corresponding story in the manga; according to an interview I read somewhere, they were basically filler eps, introducing the viewer to the three main characters of the series: Vash the Stampede, Meryl Strife, and Milly Thompson. These are fun episodes, all comedy with the occasional melodrama, and the hint that there's something else under that tall blonde man's goofy exterior. The pilot chapter of the manga corresponds with episode four, and is pretty much the same, except for a a rather major exception which, in turn, changes a few other things: there's no Milly or Meryl, so Vash has to deal with the sleazy sheriff without any help from Deringer Meryl. The gun hidden in his left arm makes its first appearence, which he uses to basically cow the bad guy into submission.

In the manga, there's a "0" chapter, that briefly speaks of July, giving the time and day it was destroyed. We see the ruined city and the figure wrapped in a tattered poncho, but that's it.

Chapter one of volume one corresponds to episode five of the anime, with some elements of episode one (Milly and Meryl in the bar, asking questions about Vash the Stampede). Because in the manga this is the first appearence Milly and Meryl make, Meryl doesn't have her moment of shocked epiphany as she makes the connection between the guy in the red coat and the legendary outlaw. Basically, the first time she sees him (in the manga) is when he's in his serious mode, gunfighting. Most of the things I liked in this story were kept, whether I read the manga or watch the anime - but in the end, I think I like the anime version better. There was more of a buildup than there was in the manga (the story editor of the anime admitted that it was his idea to have Vash fire his first shot in episode five), and Vash's grim determination ("until the day I meet him again ...") is much more dramatic when you consider what he's been like for the previous four episodes of the anime. I also liked better that, in the anime, Gofsef fires at the unconscious women, rather than at Vash - call me odd, but I thought it had more impact, with Vash having to run, draw his gun, and fire to protect others, rather than just himself.

However, they kept the scene with the ketchup, Vash's rather vague comment about not stopping until he sees someone again, and Kuroneko-sama made an appearence. It's all good.

2. July and Brilliant Dynamites Neon
Episode six doesn't really have a corresponding part in the manga. There are elements of it - Milly getting drunk at Vash's party, the prostitutes, and the appearence of the sand steamer. However, Elizabeth never makes her dramatic appearence to fix April City's broken Plant, so there's no confrontation between her and Vash about the destruction of July. Also, the hints of Vash's connections to the Plants is delayed - in the manga, there's no Wild Turkey scene, or the "Vash fixes the Plant and saves the day" scene.

The majority of the Brilliant Dynamites Neon story is the same between anime and manga. Kaite still suckers Vash with his story of an abusive foster home and ends up slipping him a mickey; Vash has his dream-encounter with Rem (though in the manga, it's more of a conversation, and in the anime, it's more of her just talking to him); Vash and Neon have their showdown; and Neon and Kaite end up saving the Flourish.

A few things are noticeably different in the manga, though; in the anime, when Vash has his drug-dream, we never see Rem's face; only her back as she stands among floating red petals. In the manga, Vash wakes up on a picnic blanket, and the two actually speak back and forth before they're separated. In the anime, he tells Elizabeth that he doesn't know what happened at July - "I don't remember." In the manga, because there is no Elizabeth, he tells Neon about his lack of memory right before the two of them set out for their duel. Unlike the anime, where the only thing the people think to do is to toggle the emergency brake to stop the sand steamer from going into the canyon, there's also a plant aboard that begins to overreact. The Plant core resembles a woman with feathery hair and long wings, plus a lot of smaller, stunted winged bodies growing from her back, and another, headless body that connects "her" to the rest of the Plant. In the manga, when it starts going crazy, Vash calms it down, referring to it as a sibling. "Iyo, kyoudai," he says.

3. Legato Bluesummers and Nicholas D. Wolfwood
The situations are the same, the orders are just different. ^_^; We'll start with Legato, since he has some scenes spliced inbetween Wolfwood's introduction in the manga.

Legato Bluesummers first shows up at the end of volume two of the manga, and in episode twelve of the anime. The only major difference came in at the very end, when Legato leaves the scene and the shoemaker's wife runs in screaming. In the anime, she just babbles on about her husband was murdered and "doesn't say anything" - in the manga, she flat-out screams that his head is gone. Vash, hearing that, whirls to look at the bag Legato left behind, and there's a pool of blood seeping from the corner.

As for Wolfwood - he's introduced about halfway through volume three of the manga (after Legato and Monev the Gale) and episode ten of the anime (before the whole mess with the Gung-Ho Guns is introduced).

In both the anime and the manga, Wolfwood is introduced when Vash notices sunlight glinting off the buckles on Cross Punisher from a distance, while traveling on a bus with Milly and Meryl to May City. In the anime, it's right after the incident with B.D.N., and everyone is pretty much exhausted by their ordeal. (In fact, Meryl socks Vash a few times for being too noisy and making a nuisance of himself.) Wolfwood is rescued from the desert, introduces himself, and is shocked by the fact that he was saved by the Vash the Stampede.

That's around where differences start setting in. There's still the scene with the busdriver and the confessional, and where Wolfwood comments on Vash's smile Wolfwood sees Vash smiling after he helps some kids out and comments on it, saying how it was painful to see the emptiness and pain behind Vash's normal expression. The scene with the kids is slightly different, however; instead of a mother with two hungry kids (anime), Wolfwood ends up giving most of what remains of his money to two dirty-looking streetkids. Instead of the whole sub-ending where he and Vash accidentally stumble into the remains of a ship and Vash communicates with yet another Plant, there are scenes of Legato confronting a gang. Episode eleven, "Quick Draw," never happened in the manga.

4. Gung-Ho Guns
Legato is Knives' spokesman both in anime and manga, and in both versions, he "warns" Vash about the appearence of the Gung-Ho Guns. In both versions, Vash ends up being accused of the shoemaker's death, and while he's imprisoned, the first one, Monev the Gale, comes for him. In the manga, it's a rather tense fight scene, and because there's no manga chapter that corresponds exactly with episode seventeen (huge flashback episode), it's here, while Vash is fighting Monev, that we see exactly what happened with Rem, Knives, and Project SEEDS. (All these scenes are ones that are later used in episode seventeen: Rem telling Vash about the sleeping colonists; the destruction of Project SEEDS, and Knives' plan to create a "new world" for himself and Vash.) The manga is much more violent and bloody - in the anime, this is the first time we see the gun hidden in Vash's left arm (remember, in the manga, this was already revealed in the pilot chapter); in the manga, that left arm gets completely blown off while he's fighting Monev.