Objective: Video-assisted thoracoscopic surgery (VATS) has improved patient outcomes; however, postoperative pain remains potentially severe. The objective of this study was to compare adjunct analgesic modalities for VATS, including paravertebral nerve blockade (PVB) and thoracic epidural anesthesia (TEA). Design: Prospective, randomized trial. Setting: Large academic hospital, single institution. Participants: Adult patients undergoing VATS. Interventions: Ultrasound-guided PVB catheter, ultrasound-guided single-injection PVB, or TEA. Measurements and Main Results: Postoperative visual analog scale pain scores (at rest and with knee flexion) and opioid usage were recorded. Pain scores (with movement) for the TEA group were lower than those for either PVB group at 24 hours (p 0.008) and for the PVB catheter group at 48 hours (p = 0.002). Opioid use in TEA group was lower than that for either PVB group at 24 and 48 hours (p < 0.001) and 72 hours (p < 0.05). Single-injection PVB was faster compared with PVB catheter placement (6 min v 12 min; p < 0.001) but similar to TEA (5 min). Patient satisfaction, nausea, sedation, and 6-month postsurgical pain did not differ between groups. Conclusions: TEA led to lower pain scores and opioid requirement for VATS procedures compared with PVB techniques. Single-injection PVB was faster and equally as effective as PVB catheter, and it led to similar patient satisfaction as TEA; therefore, it should be considered in patients who are not ideal candidates for TEA.