The safety and surgical oncology of laparoscopy-assisted total gastrectomy (LATG) remain inconclusive and challenging. This study aimed to compare the short-term and long-term outcomes between LATG and open total gastrectomy (OTG) procedures. In the all-included analyses, there were 69 patients in the LATG group and 268 in the OTG group. LATG was as safe as OTG without increasing postoperative morbidity and mortality. Stage imbalance might introduce differences in the numbers of harvested lymph nodes in LATG (34.4 ± 12.0) and OTG (40.9 ± 16.9), whereas 95.7% of patients underwent D2/D2+ dissection during the LATG procedure. After a median 31 months of follow-up, the overall survival outcomes were comparable between the LATG and OTG procedures (HR = 1.16, 95% CI 0.68-1.97). Sensitivity analysis found comparable node retrieval and stage-specific or treatment-specific overall survival. A retrospective case-control study was conducted among gastric cancer patients who underwent either LATG or OTG with curative intention between June 2006 and December 2015. Data retrieval was based on the Surgical Gastric Cancer Patient Registry in the West China Hospital. The primary outcome was overall survival. The secondary outcomes were postoperative complication incidence and severity, operation duration, blood loss, number of harvested lymph nodes, and postoperative hospital stay. Matched pairwise case-control comparisons were performed as a sensitivity analysis. LATG by experienced surgeons possibly has comparable short-term surgical outcomes and long-term survival outcomes compared with OTG for gastric cancer patients. However, high-quality RCTs are necessary before confirmative judgment and recommendation as an optional treatment in general practice.