TPVB can provide effective postoperative analgesia in lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS), which may enhance respiratory mechanics and postoperative expectoration, as well as relieve inflammation and stress. These mechanisms may reduce the incidence of postoperative pulmonary complications (PPCs). This study explored whether TPVB reduces the risk of PPCs in patients undergoing VATS for lung cancer.In this dual-center trial, patients who underwent VATS for lung cancer were randomly divided into the PV group (n = 151, general anesthesia [GA] and TPVB) and the C group (n = 151, GA only). The primary outcome was the incidence of a composite of PPCs within seven days postoperatively.The incidence of PPCs within seven days postoperatively was lower in the PV group (37.7%, 57/151) compared to the C group (49.0%, 74/151), with a risk ratio of 1.59 (95% CI: 1.00 to 2.50, P=0.048). And within 8-30 days postoperatively, compared with that in the C group (33.1%, 50/151), the incidence of PPCs was lower in patients in the PV group (22.5%, 34/151), with a risk ratio of 1.70 (95% CI, 1.02 to 2.84, P=0.040). There was a significant difference in the incidence of pneumonia between the PV group (11/151, 7.3%) and the C group (35/151, 23.3%; P < 0.001), and the incidence of pneumothorax between the PV group (27/151, 17.9%) and the C group (45/151, 29.8%; P = 0.015).Compared to GA alone, TPVB combined with GA reduces the incidence of PPCs within seven days postoperatively in patients undergoing VATS for lung cancer, and this beneficial effect can last up to 30 days after surgery. A possible mechanism is that TPVB reduces acute postoperative pain in patients.© 2025 Zhu et al.