Background: Pre-exam anxiety syndrome is a common condition occurring in pre-exam students and directly affects their examination performance and physical state. Wrist-ankle acupuncture has significant therapeutic effects in treating mental disorders and may also relieve the symptoms of pre-exam anxiety syndrome. Objective: To assess the therapeutic effect of wrist-ankle acupuncture on pre-exam anxiety syndrome. Design, setting, participants and interventions: A total of 60 students who met the inclusion criteria of pre-exam anxiety syndrome were enrolled from a university in Shanghai and they were randomly divided into treatment group and control group. There were 30 cases in each group, and no case failed to follow-up. In the treatment group, wrist-ankle acupuncture was adopted to point upper 1 bilaterally (impression between flexor carpi ulnaris tendon and ulnar margin), and there was no requirement for Deqi (arrival of qi). In the control group, sham acupuncture was adopted. The treatment was applied 3 times totally in both groups one week before the exam, once every other day, each time with the needles retained for 30 min. Main outcome measures: The therapeutic effects were compared between two groups. Before and after 3 treatments, Sarason Test Anxiety Scale (TAS) and Expectation and Treatment Credibility Scale (ETCS) were measured and evaluated. Results: The therapeutic effect experienced by the treatment group was better than that of the control group (P<0.05). There were no statistically significant differences in TAS and ETCS before treatment between the two groups. The scores of TAS after treatment in two groups were higher than those before treatment (P<0.05, P<0.01). There were statistical differences in TAS absolute difference and TAS relative difference between the two groups and the treatment group had better results (P<0.05, P<0.01). After treatment, patients in the treatment group had higher scores in ETCS than those in the control group (P<0.05, P<0.01). No adverse reaction was reported. Conclusion: Wrist-ankle acupuncture can relieve the symptoms of pre-exam anxiety syndrome significantly, and this therapy is highly safe.