Abstract: Objective To investigate the effect of comprehensive nursing intervention on postpartum depression in pregnant women with high risk of pregnancy. Methods Eighty-eight patients with postpartum depression diagnosed within 2-5 days after delivery from February 2016 to February 2018 in the first affiliated hospital of Bengbu medical college were randomly divided into study group and control group, with 40 cases in each group. Patients in the control group were treated with routine nursing intervention. The patients in the study group were treated with comprehensive nursing intervention. The quality of care, depression score, anxiety score and quality of life before and after treatment were compared. Results The nursing satisfaction of the study group was higher than that of the control group (P<0.05). The nursing service level, nursing attitude, psychological intervention, and health education of the study group were significantly higher than those of the control group, the differences were statistically significant (all P<0.05). After the nursing intervention, both groups of patients had depression and anxiety scores, but there were no significant. The score of the study group was better than that of the control group (P<0.05). The quality of life of the study group was higher than that of the control group (P<0.05). The social function, physical function, the functional and cognitive functions were significantly higher than those of the control group, and the differences were statistically significant (all P<0.05). Conclusion The incidence of postpartum depression in high-risk pregnant women is higher, and the impact on maternal physical and mental health and neonatal growth is more serious. Adequate attention and nursing intervention should be given. Comprehensive nursing intervention for high-risk pregnancy patients with postpartum depression can effectively reduce the depression and anxiety scores of patients, and further improve the patients' nursing satisfaction and quality of life, which is worthy of further clinical promotion and application.