Background: Prolonged air leak after pulmonary surgery remains a clinical challenge and sometimes needs surgical reintervention. An autologous blood patch (ABP) may provide a noninvasive method to stop air leak. Its value, however, is debatable. The aim of this systematic review is to synthesize evidence regarding the efficacy of ABP in patients with prolonged air leak. Methods: A comprehensive search for published studies was performed in the Medline database, Embase, and the Cochrane library. Randomized controlled trials, case-control studies, and case series in which a postoperative ABP was performed were included. Findings from these studies were tabulated and data were synthesized graphically (PROSPERO registration number CRD42020157591). Results: A total of eight studies was included in the analysis, comprising 151 patients. Studies demonstrated heterogeneity in ABP timing and practice, and an intermediate to high risk of bias was scored. The majority of studies demonstrated a beneficial effect of the ABP, with a high rate of success of more than 89%. One randomized trial did not find a difference in time to cessation of air leak after ABP compared with conservative tube thoracostomy. The overall complication rate was 10%. Conclusions: Quality of included studies is limited owing to lack of comparison groups. Synthesized data in this review demonstrate a high rate of successful procedures and acceptable complication rates, and seems encouraging enough to justify a large randomized clinical trial on the use of ABP for patients who have prolonged air leak after thoracic surgery.