INTRODUCTION: The addition of programmed cell death protein-1 (PD-1) inhibitors to chemotherapy (CT) or anti-CTLA4 (ipilimumab) has recently emerged as an effective first-line (1L) treatment for esophageal squamous cell carcinoma (ESCC), the most common form of esophageal cancer globally. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials (RCTs) investigating 1L PD-1 inhibitor regimens in adult patients with unresectable, locally advanced, or metastatic ESCC. Bayesian NMAs were conducted to evaluate overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). RESULTS: Three eligible RCTs were identified, evaluating three PD-1 inhibitor regimens with broad regulatory approval for 1L ESCC in combination with CT (tislelizumab, nivolumab, and pembrolizumab). Tislelizumab + CT demonstrated similar long-term OS to nivolumab + CT and pembrolizumab + CT but a significant PFS benefit over nivolumab + CT and comparable efficacy to pembrolizumab + CT. Subgroup analyses were consistent with the base case, including among patients with varying PD-L1 expression (≥1% and ≥5% Tumor Area Positivity [TAP] score or ≥1 and ≥5 combined positive score [CPS]), Asia versus the rest of world, and different underlying CT backbones. Safety profiles were comparable across the three treatments. CONCLUSION: Tislelizumab + CT is an effective 1L treatment option for advanced or metastatic ESCC, demonstrating comparable efficacy and safety outcomes relative to existing treatments.