Uncharted: Drake's Fortune

NOTE: To use this method, you need to have completed the game once on any difficulty, and have at least 500 pts. in medals so that the Mk-NDI Grenades are unlocked in Rewards.

Use Chapter Select and start up Chapter 13. As soon as it starts, run straight ahead and jump in the water. Swim right, toward the bridge, and climb up on the very last low platform on the right that sticks out from the bridge. (Same place as a Treasure collectible).

Now hit pause and go to Bonuses/Rewards/Weapon Select. Make sure the Mk-NDI Grenades says "On", then press Start to exit. Even if it already says on, click on it anyway. This will give you full grenade ammo.

Now jump up and hang off the side of the bridge. Look to the right and you will see two guys there. Kill them with grenades while hanging off the bridge. Now just Restart Checkpoint. You will restart one level up from the river, so just turn left, jump down, and jump back in the water.

Rinse and repeat 4 more times until you get 10 kills in this manner and unlock your trophy.

NOTE: Save your game after getting the medal, or it may not save your medal points.

During a regular story playthrough, a good spot to farm these kills is in Chapter 9.

After the initial Jet Ski run, Elena will drop you off saying that "you gotta get to that tower". Immediately fight off the three pirates. In the same area, up the stairs opposite the flooded alley, you will find two grenades. Now, just swim the flooded alley running into the end. By not getting out of the water, you will just 'hang' there. Equip the grenades, aim and throw. Once all grenades are spent, allow yourself to be killed. You will spawn at the point where Elena dropped you off but without the initial three pirates. The two grenades will reappear.

Repeat until Trophy pops. This is a good time and spot to also work on the Hangman Trophy - shoot 10 while hanging from a ledge.

As all the other guides suggest, manually save your game to preserve your medal points.