Background: CheckMate 649 (NCT02872116) is a randomized, open-label, phase 3 study in first-line treatment of pts with advanced GC/GEJC/EAC. Primary results showed statistically significant improvement in overall survival (OS) for N+C versus C in all randomized pts. Prior analyses conducted for 24-month follow-up (FUP) showed pts receiving N+C maintained HRQOL and experienced delayed deterioration in HRQOL compared with pts receiving C. Here we report additional analyses of HRQOL with 36-month FUP data. Methods: Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga) and EQ-5D-3L results were collected at baseline (BL) and every 6 weeks while on treatment. Change from BL in FACT-Ga, EQ-5D Visual Analog Scale (VAS), and Utility Index (UI) scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement events were based on prespecified meaningful thresholds for change scores. Results: A total of 1,581 pts were randomized to N+C (n = 789) and C (n = 792); of those, 1,360 pts had BL and post-BL PROs and were included in the PRO population (N+C [n = 694] and C [n = 666]). With additional follow-up, least-squares mean differences from BL remained comparable between groups across visits for HRQOL measurements with exceptions. FACT-Ga total score, GaCS, physical well-being (WB), and emotional WB tended to favor N+C; social WB tended to favor C. For all randomized pts, most time-to-event endpoints favored N+C; like the 24-month analysis, statistically significant delays in deterioration were maintained for TuDD (except FACT-G Social WB) and TTSD (only FACT-GaCS and FACT-Ga total). Conclusions: These results confirm the earlier 24-month FUP findings. Compared with C alone, N+C maintained HRQOL with decreased risk of deterioration in pts with previously untreated advanced or metastatic GC/GEJC/EAC. Together with improved OS, data continue to support N+C as a first-line standard treatment for GC/GEJC/EAC. Clinical trial information: NCT02872116.