Background: For advanced gastric cancer (AGC), D2 gastrectomy is the standard treatment worldwide, and this procedure shows improved survival. One systematic review and several retrospective studies showed that overall survival rate and disease-free survival following laparoscopic D2 gastrectomy for AGC was not significantly different from ODG. In addition, we showed that the compliance rate of D2 lymph node dissection in LADG was not different from that in ODG in gastric cancer patients. Laparoscopic D2 gastrectomies are technically challenging, and their oncologic safety has not been proven by a prospective randomized controlled trial. This study was a multicenter, prospective, randomized phase II study to evaluate the feasibility of LADG with D2 lymph node dissection compared with ODG for AGC treatment. Methods: Patients with cT2-T4a and cN0-2 (AJCC 7^thstaging system) distal gastric cancer were randomly but not blindingly assigned to LADG or ODG groups using fixed block sizes with a 1:1 allocation ratio. The primary endpoint was the noncompliance rate of the lymph node dissection, which was used to evaluate feasibility. Secondary endpoints included 3-year disease-free survival, 5-year overall survival, complications, and surgical stress response. Results: Between Jun 2010 and Oct 2011,204 patients were enrolled and underwent either LADG (n = 105) or ODG (n = 99). Of those, 196 patients (100 in LADG and 96 in ODG) were included in the intention-to-treat analysis. There were no significant differences in the overall noncompliance rate of lymph node dissection between LADG and ODG groups (47.0% and 43.2%, respectively; p = 0.648). In the subgroup analysis, the noncompliance rate in the LADG group was significantly higher than in the ODG group for clinical stage III disease (52.0% vs. 25.0%, p = 0.043). Three-year disease-free survival was not different in between the groups (LADG, 80.1%; ODG, 81.9%; p = 0.448). Postoperative complication rate and surgical stress response were not different between the groups. Conclusions: LADG was feasible for AGC treatment based on the noncompliance rate of D2 lymph node dissection. Clinical trial information: NCT01088204