Objective To observe the clinical efficacy and safety of repeated transcranial magnetic stimulation combined with escitalopram in the treatment of senile depression. Methods A retrospective analysis of clinical data from 80 elderly patients with depression in our hospital from March 2016 to March 2019 randomly divided into observation group and control group according to different treatment regimens, 40 cases in each group, was performed. The control group was treated with escitalopram. The observation group was combined with transcranial magnetic stimulation on the basis of the control group. The Barthel index, the quality of life comprehensive assessment questionnaire (GQOLI-74) score of the two groups before and after treatment, and negative cognitive processing bias questionnaire (NCPBQ) was used to assess the severity of negative cognitive bias, and the adverse reactions were measured with symptom scale (TESS). Results After treatment, the percentage of patients with mild Barthel index in the observation group was higher than that in the control group, and the difference between the groups was statistically significant (P < 0.05). There was no significant difference in the quality of life scores between the two groups before treatment (P > 0.05). After treatment, the scores of life quality in the observation group were higher than those in the control group (P < 0.05). There was no significant difference in NCPBQ scores between the two groups (P > 0.05). The four parameters of NCPBQ scores in the observation group were significantly lower than those in the control group (P < 0.05). In the observation group, 1 patient developed dizziness, 1 patient developed nausea, 1 patient developed sleepiness, and the incidence of adverse reactions was 7.5% (3/40). In the control group, 2 patients developed dizziness, 1 patient with nausea and dry mouth, and 2 patients. The incidence of adverse reactions was 15% (6/40); the incidence of adverse reactions in the observation group was lower than that of the control group (χ2 = 5.271, P < 0.05). Conclusion Repetitive transcranial magnetic stimulation combined with escitalopram in the treatment of senile depression has a significant clinical effect, which can significantly improve clinical symptoms, negative cognitive bias, and quality of life, and has higher safety.