To observe the effect of acupuncture on patients with post stroke depression. Methods: A total of 90 patients were randomly divided into combined treatment group, acupuncture group, fluoxetine hydrochloride group and there were 30 cases in each group. The acupuncture group received acupuncture treatment on Baihui, Fengfu, Shenting, Shuigou, Dazhui, Shendao and other acupoints, once a day, 5 times a week. Fluoxetine hydrochloride group was given fluoxetine hydrochloride, 3 tablets each time, 3 times daily. Comprehensive group receive treatment combined acupuncture and fluoxetine hydrochloride. All of three groups received treatment for 3 weeks of a course, a total of 6 courses of treatment. The clinical efficacy, Hamilton Depression Rating Scale(HAMD)score, and the adverse reactions were compared in the three groups. Results: The total efficiency rate of the comprehensive group was 96.7%(29 / 30), better than acupuncture group of 83.3%(25 / 30)and fluoxetine hydrochloride group 80.0%(24 / 30). The HAMD scores in 3 groups was significantly reduced(P<0.05)after 4 weeks, 12 weeks, 24 weeks of treatment. The comprehensive group at each time point were lower than the other two groups(P<0.05); after 4 weeks and 12 weeks of treatment the acupuncture group and fluoxetine hydrochloride group showed no statistical significance(P>0.05)and after treatment of 24 weeks, the acupuncture groups HAMD score became lower than fluoxetine hydrochloride group(P<0.05). There were 2 cases of adverse reactions in the comprehensive group, 6 cases in fluoxetine hydrochloride group, and acupuncture group had no cases showing adverse reactions. Conclusion: Acupuncture treatment combined with oral Deanxit treatment has better clinical efficacy than only oral fluoxetine hydrochloride treatment or just acupuncture treatment. Acupuncture treatment while had no significant difference comparing to fluoxetine hydrochloride treatment in clinical curative effect, but long-term HAMD score and safety is superior to fluoxetine hydrochloride treatment.