Background: Over 50 % of patients with major depressive disorder (MDD) either do not tolerate or do not respond to antidepressant medications. Several preliminary studies have shown the benefi ts of acupuncture in the treatment of depression. We sought to determine whether a 2-point electroacupuncture protocol (verum acupuncture) would be benefi cial for MDD, in comparison to needling at nonchannel scalp points with sham electrostimulation (control acupuncture). Method: Fifty-three subjects aged 18–80 years, recruited via advertisement or referral, were included in the primary analysis of our randomized controlled trial, which was conducted from March 2004 through May 2007 at UPMC Shadyside, Center for Complementary Medicine, in Pittsburgh, Pennsylvania. Inclusion criteria were mild or moderate MDD (according to the Structured Clinical Interview for DSM-IV Axis I Disorders) and a score of 14 or higher on the Hamilton Depression Rating Scale (HDRS). Exclusion criteria included severe MDD, seizure disorder or risk for seizure disorder, psychosis, bipolar disorder, chronic MDD, treatment-resistent MDD, and history of substance abuse in the prior 6 months. Patients were randomized to receive twelve 30-minute sessions of verum versus control acupuncture over 6 to 8 weeks. The HDRS was the primary outcome measure. The UKU Side Eff ect Rating Scale was used to assess for adverse eff ects. Results: Twenty-eight subjects were randomized to verum electroacupuncture and 25 to control acupuncture. The 2 groups did not diff er with regard to gender, age, or baseline severity of depression. Both groups improved, with mean (SD) absolute HDRS score decreases of –6.6 (5.9) in the verum group and –7.6 (6.6) in the control group, corresponding to 37.5 % and 41.3 % relative decreases from baseline. There were no serious adverse events associated with either intervention, and endorsement of adverse eff ects was similar in the 2 groups. Conclusions: We were unable to demonstrate a specifi c eff ect of electroacupuncture. Electroacupuncture and control acupuncture were equally well tolerated, and both resulted in similar absolute and relative improvement in depressive symptoms as measured by the HDRS. TRIAL REGISTRATION: clinicaltrials.gov Identifi er: NCT00071110.