Objective: To comparatively analyze the long-term efficacy and safety of laparoscopic radical resection and laparotomy for locally advanced gastric cancer, providing evidence-based medical evidence for the selection of clinical treatment plans. Methods: A retrospective selection of 150 patients with locally advanced gastric cancer who underwent surgical treatment in our hospital from October 2021 to October 2022 was made as the research subjects. They were divided into a laparoscopic group (120 cases) and a laparotomy group (30 cases) based on the surgical approach. The laparoscopic group underwent laparoscopic radical gastrectomy, while the laparotomy group underwent traditional laparotomy radical gastrectomy. We compared the perioperative indicators and the occurrence of postoperative complications between the two groups of patients, and conducted a 3-year follow-up to compare the 3-year overall survival rate (OS), disease-free survival rate (DFS), and tumor recurrence and metastasis between the two groups. Results: The intraoperative blood loss, postoperative exhaust time, postoperative hospital stay, and incision length of patients in the laparoscopic group were significantly better than those in the open surgery group (all p < 0.001). The operation time in the laparoscopic group was longer than that in the open surgery group (p < 0.001). The overall incidence of postoperative complications in the laparoscopic group was significantly lower than that in the open surgery group (p = 0.014 < 0.05). The 3-year overall survival (OS) and 3-year disease-free survival (DFS) rates in the laparoscopic group were higher than those in the open surgery group, while the local recurrence rate and distant metastasis rate were lower than those in the open surgery group, with no statistically significant differences between the two groups (all p > 0.05). Conclusion: Laparoscopic radical gastrectomy for locally advanced gastric cancer offers advantages such as reduced intraoperative bleeding, faster postoperative recovery, and fewer complications. Its long-term efficacy is comparable to that of open surgery. Therefore, under strict adherence to surgical indications, laparoscopic radical gastrectomy can be considered one of the preferred treatment options for locally advanced gastric cancer.