Background <p>Although the association between institutional surgical volume and outcomes is well established in highly complex procedures, evidence in thoracic surgery remains inconsistent. Uniportal thoracoscopic major pulmonary resection is technically demanding, and the impact of institutional experience on perioperative outcomes has not been fully clarified. This study investigated the relationship between institutional volume and perioperative outcomes, focusing on procedure-related complications.</p> Methods <p>This nationwide multi-institutional retrospective cohort study included patients who underwent uniportal thoracoscopic lobectomy or segmentectomy at 43 Japanese institutions between April&#xa0;2018 and March&#xa0;2023. Institutions were categorized into low-, middle-, and high-volume groups based on total case volume. Stabilized inverse probability of treatment weighting (IPTW) was applied to adjust for baseline differences. The primary endpoint was surgical procedure-related complications, categorized as intraoperative events, technical postoperative complications, and early reintervention.</p> Results <p>A total of 3969 patients were analyzed. After stabilized IPTW, a significant global difference in surgical procedure-related complications was observed among the three institutional volume groups (<i>P</i> = 0.047). Post-hoc analyses demonstrated a significantly lower risk of intraoperative significant vessel injury in the High-volume group compared with the Low-volume group (OR 0.54, 95% CI 0.36–0.82), and a lower incidence of postoperative prolonged air leak in the High-volume group compared with the Middle-volume group (OR 0.63, 95% CI 0.47–0.84). Rare but severe complications, including bronchial fistula, empyema, and reoperation, were infrequent and did not differ among groups.</p> Conclusions <p>Higher institutional surgical volume was independently associated with reduced technique-sensitive complications in uniportal thoracoscopic major pulmonary resection.</p>