Liposomal bupivacaine (LipoB) provides prolonged local anesthetic effects and has seen usage in several fields of surgery. We review our experience using LipoB intraoperatively for intercostal nerve blocks after video-assisted throacoscopic surgery (VATS). A retrospective, single-center review was conducted for patients undergoing VATS from August 2012 to December 2014. Patients those who received LipoB as an intercostal nerve block were compared with patients who received blocks with standard bupivacaine. Opiate amounts used within the first six hours and then subsequent 18, 48, and 72 hours were converted into morphine equivalents for comparison. Forty-seven patients met inclusion criteria: 21 receiving LipoB intercostal nerve block and 26 controls. Groups were similar for age, diabetes, hypertension, chronic kidney disease, body mass index and American Society of Anesthesiologists scores. The LipoB group had a larger portion of males (P < 0.02). Postoperatively, morphine equivalent usage was significantly less in the LipoB group compared with the standard bupivacaine within the first six hours after surgery (15.62 vs 52.41, P = 0.001) and in the subsequent 18 hours (28.98 vs 65.17, P = 0.01). After the first 24 hours there was not a significant difference in opiate usage between the two groups. There was no difference in length of stay between the two groups. In our study group of VATS patients, an intercostal nerve block with LipoB significantly reduced the usage of postoperative opioids in the first 24 hours only when compared with standard bupivacaine.