OBJECTIVE: To investigate the effects of WAA combined with fluoxetine in the clinical treatment of post-stroke depression(PSD).METHODS: In this randomized, controlled and single-blind trial, 105 PSD patients who met the inclusion criteria were randomly divided into three equal groups: Thin wrist-ankle acupuncture(WAA)group(Thin WAA needle + Fluoxetine), Thick WAA group(Thick WAA needle + Fluoxetine), and Sham WAA group(sham WAA needle + Fluoxetine). In this trial, the primary outcome was Hamilton Depression Scale(HAMD), while the secondary outcomes included Zung self-rating depression scale(SDS) and World Health Organization Quality of Life BREF(QQL).RESULTS: Ninety nine PSD patients completed all the treatment. The HAMD scores and SDS scores of all the three groups decreased after treatment(P < 0.05). There was no significant difference between the QQL scores of the three groups(P >0.05). There was no significant difference in the scores of the three scales between the thick wrist ankle needles and the thin wrist ankle needles(P >0.05).CONCLUSION: The present study showed that WAA combined with fluoxetine can relieve the symptoms of depression after stroke. WAA therapy could improve the antidepressant effect of fluoxetine.