Importance No prospective trial on laparoscopy has been specifically designed for clinical T4a gastric cancer (GC); evidence of the safety and efficacy of laparoscopy for T4a GC is currently insufficient. Objective To compare the short-term surgical outcomes between laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) with D2 lymph node dissection for patients with clinical T4a GC. Design, Setting, and Participants The UMC-UPPERGI-01 randomized clinical trial (RCT) was a single-center, open-label, noninferiority RCT conducted at a tertiary hospital in Ho Chi Minh City, Vietnam, among patients with clinical T4a GC. The study was conducted from June 2020 to April 2025. Interim and short-term results analyses were conducted in October 2023 and June 2025, respectively. Interventions Patients were randomly assigned 1:1 to undergo LDG or ODG with D2 lymph node dissection as the full analysis set of the UMC-UPPERGI-01 trial. The procedures were performed exclusively by qualified surgeons. Main Outcomes and Measures Short-term outcomes included surgical results, pathological characteristics, 30-day postoperative morbidity and mortality (Clavien-Dindo classification), and postoperative recovery parameters. Results A total of 208 patients who underwent curative-intent distal gastrectomy with D2 lymphadenectomy were included in the full analysis set, with 104 patients in each group. There was no crossover between the 2 groups. Patients in the LDG group had a mean (SD) age of 61.1 (10.0) years and included 25 female patients (24.0%). Patients in the ODG group had a mean (SD) age of 60.0 (10.7) years and included 29 female patients (27.9%). No significant differences were found between the LDG and ODG groups in 30-day morbidity and mortality, including rates of any postoperative complication (22.1% vs 21.2%; P = .87) and severe complications (2.9% vs 3.8%; P &gt; .99). The LDG group showed nonsignificant differences regarding surgical complications (21.2% vs 16.4%; P = .37) and general complications (3.9% vs 10.6%; P = .11) compared to the ODG group. The LDG group had significantly longer mean (SD) operative time (220.0 [42.4] minutes vs 153.7 [36.7] minutes; P &lt; .001) and higher median (IQR) blood loss (80 [50-145] mL vs 50 [30-100] mL; P = .003). There were no significant differences in terms of time to the first flatus, time to oral tolerance, length of postoperative hospital stay, and time from surgery to initiation of adjuvant chemotherapy. Comorbidity was identified as an independent risk factor for postoperative complications in multivariate analysis (odds ratio, 2.42; 95% CI, 1.11-5.30; P = .03). Conclusions and Relevance In the UMC-UPPERGI-01 noninferiority RCT, LDG showed comparable short-term outcomes to ODG for T4a GC. The results suggest that LDG can be recommended as an alternative to ODG by qualified surgeons for clinical T4a GC; ongoing follow-up will determine long-term oncologic outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT04384757