Background Endobronchial valves had been utilized for many years to treat patients with advanced emphysema, despite unfavorable results. In this meta-analysis, we aimed to assess the efficacy and safety of the use of endobronchial valves in patients with heterogeneous advanced emphysema. Methods We performed systematic database searches to identify clinical trials that met all our inclusion criteria. Direct-comparison and mixed-treatment-comparison (MTC) meta-analyses were conducted to estimate the mean difference or odds ratio of outcomes. Each outcome was analyzed with Review Manager 5 statistical software. Results Eight prospective clinical trials assessing this therapy were retrieved, with a total of 744 patients. Outcomes, including the forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT), and St. George's Respiratory Questionnaire (SGRQ), were analyzed, and the odds ratio of reported complications related to endobronchial valve therapy was calculated. Significant improvement in the mean difference of FEV1 (5.61 [4.42, 6.80]), 6MWT (25.75 [12.30, 39.20]), and SGRQ (-10.96 [-13.88, -8.05]) was observed after endobronchial valve treatment. Moreover, the rate of adverse events related to endobronchial valves was low. Conclusions Endobronchial valve treatment offers benefits in terms of lung function and quality of life. Endobronchial valve treatment is feasible and safe for patients with advanced heterogeneous emphysema, especially those with no evidence of collateral ventilation.