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Introduction: The best treatment for advanced, PD-L1-high non-small-cell lung cancer remains a debated issue. Methods: A meta-analysis of randomized clinical trials (RCTs) was performed to compare the efficacy and safety of PD(L)1 inhibitors alone or plus chemotherapy (CT) for advanced, PD-L1-high non-small-cell lung cancer. Results: 14 RCTs were included. The combination of a PD(L)1 inhibitor with CT resulted in the improvement of progression-free survival (HR: 0.59; 95% CI: 0.43–0.79; p = 0.0005) and objective response rate (RR: 1.66; 95% CI: 1.14–2.42; p = 0.008). No overall survival difference was documented (HR: 0.99; 95% CI: 0.77–1.27; p = 0.95). The risk of grade ≥3 treatment-related adverse events was significantly reduced with immune-checkpoint inhibitor single-agent therapy compared with immune-chec…