<sec><title>Objective</title> To explore the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on depression, cognitive function and activities of daily living in patients with depression after cerebral infarction. </sec><sec><title>Methods</title> A total of 50 patients with depression after cerebral infarction from the departments of neurology and rehabilitation of the Second Affiliated Hospital of Chongqing Medical University from July 2018 to February 2020, which were randomly divided into the control group and the observation group, with 25 cases in each group. All of the patients received conventional drug therapy, rehabilitation training, and paroxetine antidepressant treatment. On this basis, the control group was given sham stimulation, the coil of magnetic stimulation was placed at 90 degrees perpendicular to the scalp, the stimulation frequency was 10.0 Hz, the stimulation intensity was 80%-90% resting motor threshold (RMT), and the stimulation intensity was adjusted from low to high according to the patients tolerance, two seconds per stimulus, 20 seconds interval, total pulses 1 200, once a day, five days a week, continous treatment for six weeks. The observation group was given high-frequency rTMS treatment, the stimulation site was the left dorsolateral prefrontal cortex (DLPFC), the center point of the coil was tangent to the patients scalp surface, and the treatment parameters and time were the same as those in the control group. Before treatment and after treatment for six weeks, the Montreal cognitive assessment scale (MoCA) was used to evaluate the overall cognitive function of patients; the Hamilton depression scale (HAMD) was used to evaluate the depression of patients; the modified Barthel index (MBI) was used to evaluate the activities of daily living of patients; the auditory event-related potential P300 was used to evaluate cognitive function and the adverse reactions of the two groups were compared. </sec><sec><title>Results</title> There were no significant differences in MoCA, HAMD, MBI scores and P300 between the two groups before treatment (<italic>P</italic>>0.05). Compared with before treatment, MoCA scores, subitem scores of MoCA (such as visuospatial/executive function, attention/calculation) and MBI score of both groups after treatment for six weeks were significantly higher (<italic>P</italic><0.05), HAMD score and P300 latency of both groups were significantly lower, the difference was statistically significant (<italic>P</italic><0.05). Compared with the control group, the MoCA scores and subitem scores of MoCA (such as attention/calculation and delayed memory) of the observation group were significantly higher (<italic>P</italic><0.05), and HAMD score and P300 latency were significantly lower, the difference was statistically significant (<italic>P</italic><0.05). There were no significant differences in MBI score and occurrence of adverse events between the two groups (<italic>P</italic>>0.05). </sec><sec><title>Conclusion</title> High frequency rTMS can effectively improve the depressive state and cognitive function of patients with post-stroke depression, which is worthy of clinical application. </sec>