Background: The safety of laparoscopic gastrectomy for advanced gastric cancer is controversial. We conducted a multi-institutional, randomized controlled trial to compare short- and long-term outcomes of laparoscopic distal gastrectomy (LAP) with D2 lymph node dissection for advanced gastric cancer in comparison to open distal gastrectomy (OP) in Japan (UMIN000003420). We herein demonstrate short-term outcomes of this trial. Methods: Patients with potentially curable gastric cancer (T2-T4, N0-2 and M0) by distal gastrectomy were eligible for inclusion. Between November 2009 and July 2016, 507 patients were randomly assigned to either the LAP group (n = 252) or the OP group (n = 255). Only credentialed surgeons in both the procedures from 37 Japanese institutions participated in the study. The primary endpoint was 5-year relapse free survival. Secondary endpoints were 5-year overall survival, adverse events and short-term clinical outcomes. Results: According to study protocol, 47 patients among the total eligible patients were excluded because of distant metastasis or tumor extension intraoperatively. The remaining 460 patients underwent distal gastrectomy with D2 lymph node dissection and were analyzed as per protocol. Estimated blood loss was lower in LAP than in OP (30 vs. 150 ml, P < 0.001) and operative time was longer in LAP than in OP (291 vs. 205 min, P < 0.001). Post-operative analgesics use was less in LAP than in OP (38.3 vs. 53.6 %, P = 0.001), and first day of flatus was shorter in LAP than in OP (2 vs. 3 days, P < 0.001). There were no significant differences in all grade intra-operative complications (LAP 0.9% vs. OP 2.6%, P = 0.285). In addition, there were no significant differences in grade 3 and higher post-operative complications between the two groups (LAP 3.1% vs. OP 4.7%, P = 0.473). Hospital mortality was 0.4 % in each group. Conclusions: Credentialed surgeons could safely perform laparoscopic distal gastrectomy with D2 lymph node dissection for locally advanced gastric cancer. The laparoscopic approach could be accepted without increasing major surgical complications in this setting. Clinical trial information: 000003420.