Context center dot Gynecological malignancies can pose a serious threat to women's physical and mental health, and lymphedema is one of the common complications after surgery for malignant tumors. Comprehensive nursing might be able to reduce the lymphedema that occurs after surgery and help accelerate patients' postoperative rehabilitation process. Objective center dot The study intended to explore the effects of a comprehensive nursing intervention for patients with lower-limb lymphedema after surgery for malignant gynecological tumors. Design center dot The research team performed a retrospective controlled study. Setting center dot The study took place at Sichuan Cancer Hospital in Chengdu, China. Participants center dot Participants were 90 patients who received surgical treatment at the hospital for malignant gynecological tumors between April 2020 and July 2021. Intervention center dot The research team divided participants into two groups: (1) 45 in the intervention group who received a comprehensive nursing intervention based on a metaheuristic learning model, and (2) 45 in the control group, who received routine nursing. The nursing intervention occurred for both groups for one year, from admission for surgery, baseline, to the end of treatment, postintervention. Outcome Measures center dot The research team: (1) assessed the efficacy postintervention of the nursing intervention for the two groups, (2) measured the circumference of participants' lower-limb edema at baseline and postintervention, (3) determined the incidence of lymphedema between baseline and postintervention in the two groups, (4) measured the nursing satisfaction scores of the two groups postintervention, and (5) evaluated participants' quality of life using the Abbreviated World Health Organization Quality-of-Life (WHOQOL-BREF) scale at baseline and postintervention. Results center dot Postintervention: (1) the efficacy of the nursing intervention for the intervention group was 95.56%, which was a significantly higher rate than that of the control group, at 82.22% (P = .044); (2) the intervention group's decrease in the mean circumference at 10 cm below the knee was significantly greater, from 40.43 +/- 1.75 cm to 34.93 +/- 1.94 cm, than that of the control group, from 39.93 +/- 2.01 cm to 35.89 +/- 2.27 cm (P = .034), and that group's decrease in the mean circumference at 10 cm above the knee was also significantly greater, from 49.50 +/- 3.06 cm to 44.12 +/- 2.14 cm, than that of the control group, from 49.13 +/- 3.11 cm to 46.10 +/- 1.94 cm (P < .001); (3) of the 45 participants in the intervention group, only one had lymphedema (2.22%), which was a significantly lower rate than that of the control group, at six participants out of 45 (13.33%), with P = .049; (4) the intervention group's mean score for nursing satisfaction was 86.59 +/- 3.96, which was significantly higher than that of the control group, at 82.22 +/- 5.61 (t = 4.269, P < .001); and (5) the intervention group's mean score on the WHOQOL-BREF scale was 25.52 +/- 2.94, which was significantly higher than that of the control group, at 22.28 +/- 3.00 (t = 5.174, P < .001). Conclusions center dot A comprehensive nursing intervention after surgery for patients with gynecological malignancies can reduce the incidence of lymphedema, be more effective, and enhance patients' satisfaction with nursing care and their quality of life.