Abstract This systematic review summarizes existing evidence for superior onset, quality, and duration of block for ultrasound guidance versus other techniques for nerve localization. MEDLINE was systematically searched from 1966 to June 2013 for randomized controlled trials (RCTs) comparing ultrasound guidance to another technique for peripheral nerve blocks. Twenty-three RCTs were identified for upper-extremity peripheral nerve blocks and 17 for lower extremity. Jadad scores for quality of RCT ranged from 1 to 5 with a median of 3. For upper-extremity blocks, 11 (48%) of 23 RCTs reported faster onset of block, 9 (39%) of 23 reported better quality of block, and 1 (14%) of 7 reported longer duration of block with ultrasound. One RCT reported that ultrasound was inferior for onset of combined median and ulnar block. For lower-extremity blocks, 8 (80%) of 10 RCTs reported faster onset, 9 (56%) of 16 reported better quality, and 2 (33%) of 6 RCTs reported longer duration of blocks. One RCT reported that ultrasound was inferior for quality and duration for ankle block. There is level 1b evidence to make a grade A recommendation that ultrasound guidance provides a modest improvement in block onset and quality of peripheral nerve blocks, especially for lower extremity. Ultrasound is rarely inferior to other techniques.