Background It is unknown whether D2 lymphadenectomy + complete mesogastric excision for gastric cancer improves survival compared with just D2 lymphadenectomy.Methods Between September 2014 and June 2018, patients with advanced gastric cancer were randomly assigned (1 : 1) to laparoscopic D2 lymphadenectomy or D2 lymphadenectomy + complete mesogastric excision gastrectomy. The modified intention-to-treat population was defined as patients who had pathologically confirmed gastric adenocarcinoma (pT1 N1-3 M0 and pT2-4 N0-3 M0). The primary endpoint was 3-year disease-free survival. Secondary endpoints were the recurrence pattern and overall survival.Results The median follow-up of patients in the D2 lymphadenectomy group (169 patients) and patients in the D2 lymphadenectomy +complete mesogastric excision group (169 patients) was 55 (interquartile range 37-60) months and 51 (interquartile range 40-60) months respectively. Recurrence occurred in 50 patients in the D2 lymphadenectomy group (29.6%) versus 33 patients in the D2 lymphadenectomy + complete mesogastric excision group (19.5%) (P = 0.032). The 3-year disease-free survival was 75.5% (95% c.i. 68.3% to 81.3%) in the D2 lymphadenectomy group versus 85.0% (95% c.i. 78.7% to 89.6%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.042). The HR for recurrence in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 0.99) by Cox regression (P = 0.045). The 3-year overall survival rate was 77.5% (95% c.i. 70.4% to 83.1%) in the D2 lymphadenectomy group versus 85.8% (95% c.i. 79.6% to 90.2%) in the D2 lymphadenectomy + complete mesogastric excision group (log rank P = 0.058). The HR for death in the D2 lymphadenectomy + complete mesogastric excision group versus the D2 lymphadenectomy group was 0.64 (95% c.i. 0.41 to 1.02) (P = 0.058).Conclusion Compared with conventional D2 dissection, D2 lymphadenectomy + complete mesogastric excision is associated with better disease-free survival, but there is no statistically significant difference in overall survival.Registration number NCT01978444 (http://www.clinicaltrials.gov). Compared with conventional D2 dissection, D2 + complete mesogastric excision shows favourable oncological outcomes in curable advanced gastric cancer.