e16083 Background: The standard care for locally advanced gastric (LAGC) or gastroesophageal junction (GEJ) cancer is perioperative chemotherapy (CTX) with surgery. The therapeutic landscape has evolved with PD-1 and PD-L1 inhibitors, showing promise in advanced or metastatic disease. Investigating their role in locally advanced disease is an active research area. In response, we conducted a meta-analysis to evaluate the effectiveness of perioperative immunotherapy with CTX in LAGC/GEJ patients. Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing perioperative PD-1 and PD-L1 inhibitors in combination with CTX versus CTX alone for LAGC/GEJ. Evaluated outcomes included pathological complete response (pCR), R0 resection rate, downstaging rate, and treatment-related adverse events (TRAE) with a grade ≥ 3. Heterogeneity was assessed using I2 statistics, employing a random-effects model for analysis. Statistical analyses were performed using R software version 4.3.2. Results: Among 2,452 patients from six RCTs, 1,228 (50.08%) received immunotherapy. Combining immunotherapy with CTX showed substantial improvements in pCR (RR 2.83; 95% CI 1.78-4.50; p < 0.001). This effect persisted in the FLOT CTX subgroup (RR 2.15; 95% CI 1.37-3.38; p < 0.001). Additionally, downstaging outcomes were superior in the immunotherapy group, with ypT0 (RR 1.96; 95% CI 1.50-2.55; p < 0.001) and ypN0 (RR 1.36; 95% CI 1.19-1.54; p < 0.001). However, no significant differences were observed in the R0 resection rate (RR 1.01; 95% CI 0.98-1.04; p = 0.603) and TRAE grade 3 or higher (RR 1.05; 95% CI 0.98-1.13; p = 0.177). Conclusions: These findings emphasize the effectiveness of combining PD-1 and PD-L1 inhibitors with CTX, indicating an improved pathological response compared to CTX alone. As expected, these positive outcomes persisted in the FLOT regimen. Our results provide evidence supporting the combination of immunotherapy and CTX as a perioperative treatment option for LAGC/GEJ patients.