Background: Because of limitations in previous randomised controlled trials and observational studies, the effectiveness of immediate video-assisted thoracoscopic surgery (VATS) for patients with empyema in real-world settings remains unclear. Objective: This study aimed to evaluate whether immediate VATS improves clinical outcomes in patients with empyema. Methods: This multicentre retrospective cohort study included 744 patients with physician-diagnosed empyema from six hospitals between 2006 and 2021. The exposure was VATS performed within 3 days of empyema diagnosis, the primary outcome was 30-day mortality, and secondary outcomes were 90-day mortality, length of hospital stay, and time from diagnosis to discharge. We used propensity score weighting to account for potential confounders. For outcome analyses, we used logistic regression for mortality outcomes and gamma regression for the number of days. Results: Among the 744 patients, 53 (7.1%) underwent VATS within 3 days, and 691 (92.9%) initially received conservative treatment. After propensity score weighting, the differences in 30- and 90-day mortalities between the immediate VATS and initial conservative treatment groups were 1.18% (95% confidence interval [CI], −10.7 to 13.0%) and −0.08% (95% CI, −10.3 to 10.2%), respectively. The differences in length of hospital stay and time from diagnosis to discharge were −3.22 (95% CI, −6.19 to −0.25 days) and −5.04 days (95% CI, −8.19 to −1.90 days), respectively. Conclusions: Our real-world study showed that immediate VATS reduced the length of hospital stay and the time from diagnosis to discharge. Considering the small sample and differences in protocols between countries, further large-scale studies are warranted.