Background: The long-acting preparation of bupivacaine, liposomal bupivacaine (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA), was approved by the Food and Drug Administration in October 2011 and has been shown to be safe in breast augmentation. It remains to be established if liposomal bupivacaine provides superior pain control in this setting. Objectives: This study compares liposomal bupivacaine and standard bupivacaine for postoperative pain control. Methods: Thirty-four patients undergoing cosmetic primary subpectoral breast augmentation were recruited. Each patient was treated with bupivacaine in one implant pocket and liposomal bupivacaine in the other prior to closure in a randomized fashion. Both patient and surgeon were blinded. A brief pain inventory was administered by telephone every 12 h up to 72 h postoperatively. Results: Liposomal bupivacaine demonstrated a statistically significantly lower pain score at the 12, 36, and 48 h time points in the worst pain category, at the 24, 36, 48, and 60 h time points in the least pain category, at the 12, 24, 36, 48, 60, and 72 h time points in the average pain category, and at the 24, 48, and 72 h time points in the pain rated at the time of the survey. These differences, however, were small, ranging from 0.08 to 0.98 using a 10-point pain scale. When asked if the additional charge for the liposomal bupivacaine would have been worth the benefit, 70% of the patients surveyed said "no." Conclusions: Although there is a statistically significant decrease in postoperative pain with the use of liposomal bupivacaine, this may not translate to an appreciable clinical benefit that justifies the additional cost.