Background Serratus anterior plane (SAP) block is a relatively novel technique that can block the lateral cutaneous branches of the intercostal nerves as well as the long thoracic nerve. Purpose Our study aimed to evaluate the effects of SAP block on postoperative pain after thoracoscopic surgery compared with local anesthetic (LA) infiltration. Patients and methods Forty adult patients undergoing video-assisted thoracic surgery were randomized to receive either SAP block (n=20) or LA infiltration of incision (n=20). The primary outcome was postoperative visual analog scale (VAS) score at the 2nd, 8th, 16th, 24th, and 48th hour after surgery. The secondary outcomes were the consumption of sufentanil at 8th, 16th, 24th hours postoperative. In addition, rescue analgesia, drug-related adverse effects after surgery was also analyzed. Results The SAP group showed lower VAS scores at the 2nd hour (at rest: SAP group 11 [8–13] vs LA group 28 [26–32], P =0.01; on coughing: 15 [13–18] vs 33 [26–38], P =0.01) and the 8th hour (at rest: 13 [12–18] vs 36 [32–46], P =0.01; on coughing: 19 [16–23] vs 42 [36–53], P =0.01) after surgery. Postoperative sufentanil consumption in the SAP group during 0–8 hrs was significantly lower compared with the LA group ( P <0.01). The use of rescue analgesia was also significantly lower in the SAP group ( P =0.02) during 0–12 hrs. Conclusion Compared to LA infiltration, ultrasound-guided SAP block may provide better pain relief as well as reduce opioid consumption after thoracoscopic surgery.