Objective To investigate the clinical effects and safety differences of open surgery and laparoscopy primary lesion resection combined with D2 lymph node dissection in the treatment of elderly patients with advanced gastric cancer. Methods One hundred and forty elderly patients with advanced gastric cancer were chosen and randomly divided into two group including open operative group (70 patients) with primary lesion resection combined with D2 lymph node dissection by open operation and laparoscopic surgery group (70 patients) with primary lesion resection combined with D2 lymph node dissection by laparoscopy; and the operative time, intraoperative bleeding amount, the levels of PaCO2 in operation, liquid diet eating time, postoperative anal exhaust time, postoperative gastric tube indwelling time, postoperative ambulation time, the level of haemoglobin (Hb) after operation, the hospitalization time, the number of lymph node dissection, the survival rate with followed-up and postoperative complication incidence of both groups were compared. Results There was no significant difference in the operative time between 2 groups (P>0.05). The intraoperative bleeding amount, the level of PaCO2 in operation, liquid diet eating time, postoperative anal exhaust time, postoperative gastric tube indwelling time, postoperative ambulation time, the level of Hb after operation and the hospitalization time of laparoscopic surgery group were significantly better than open operative group (P<0.05). The level of PaCO2 in operation of laparoscopic surgery group was significantly higher than open operative group (P<0.05). There were no significant difference in the gastric lymph node dissection number and the peripheral lymph node dissection number of gastric artery between 2 groups (P>0.05). There were no significant difference in the survival rates between the 2 groups after 3-year followed-up (P>0.05). The complication incidence after operation of laparoscopic surgery group was significantly lower than open operative group (P<0.05). The quality of life scores of patients in laparoscopic surgery group were significantly higher than those in open operative group on 7 days and in 3 months after operation, and the difference were statistically significant (P<0.05). Conclusion Compared with open operation, primary lesion resection combined with D2 lymph node dissection by laparoscopy in the treatment of elderly patients with advanced gastric cancer can efficiently possess the advantages including minimally invasive, shorter recovery time and less postoperative complications.