Vayne is a fun-to-play and hard hitting champion if built right. After significant amounts of time testing different builds, the best build is the build that takes advantage of Vayne's true damage passive. Silver Bullets makes tanks laughable. Alistar ults are non-existent. The beauty behind Vayne is that her silver bullets don't scale with anything. To Many that may seem as a negative since you can not necessarily build anything to improve it. However at rank 5, Silver Bullets does 8% plus more damage in true damage, and when facing against health stackers and tanks that makes a huge difference than any other of her skills. This guilde focuses more on how to build Vayne than a guide on how to play her.

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I use Attack Speed runes and Mana Regen yellows. Although Vayne is not very mana hungry, with the recent changes to her if tumble is used alot mana regen is going to be needed.

21/0/9 Offensive masteries
Vayne is a ranged carry and should be played like a ranged carry. Any defensive masteries are kinda a waste on her as that if you are caught out of position she is probably going to die anyways.

andis what I normally use on her. Ghost is good for mobility or to rush to teamfights in another lane, and Exhaust is nice to have for early lane domination as well as the annoying assassin champion that tries to jump you.Is also a good substitute for Exhaust, it is just a matter of preference.
All other Summoner Spells aren't recommended and if you think Revive and Heal are good then the build won't really matter then now will it.

The entire point of the build is to take advantage of Vayne's Silver Bullets by building a large amount of attack speed to get the three-hit combo as fast as possible.
Start/Early Game Build:+x3
To start off I build boots to be able to be mobile and play defensive. Since at first Vayne is fairly week with her Silver Bullets boots are necessary to be able to dodge skill shots and out-run her opponents.
After First Return:+ORHopefully when you first recall back you have amounted enough gold for a recurve bow. If not finish out your boots or work towards the type of boots you need. If there is an obnoxious amount of crowd control on the other team go ahead and go for Mercury Treads but if not stick with the Attack Speed Boots. Upon attaining the Recurve Bow your Attack Speed in combination with higher ranks of Silver Bullets you will start to make a presence in your and have alot more opportunities to get away with a three-shot combo.
After Recurve Bow:

There are a couple routes that can be taken after the Recurve Bow depending on the situation.
IF STACKING HEALTH/ALL TANK TEAM:If all of the opposing team is stacking ridiculous amounts of health than this is a must. HOWEVER I do not recommend rushing this item in any other case. After the Recurve Bow this item offers no other attack speed and costs roughly 2k gold to finish out.
IF AP HEAVY:The magic resist will be nice against an Ability Power team, and the other two options in this case will be less as effective.
IF LARGE AMOUNTS OF DODGE/ANYTHING ELSE:This is my favorite attack speed item, mainly since that attack speed is the greatest that can be taken from a Recurve Bow. The passive is a nice boost and the item effect is great against tanks and the annoying little *@&!@ of champion called Jax.
Mid Game/Late Game:
Once past the first item split the rest of the build runs the same amounting to this general build:
If the situation called for a Madred's Bloodrazer first than simply switch the order of Sword of the Divine with it and build SotD when you would have built the Madred's. Normally the game will end before fully building Madred's (if going SotD first).

So there you have it. You have just witnessed the unveiling of knowledge that has unlocked the ability to pwn and own tanks and any others that stand in your way. Vayne is a relatively difficult champion to play so if at first this build does not work for you just remember it will take a couple plays to get used to the style of play that this build requires. Please comment on this build and vote!