Objective: To learn whether metformin treatment affects oxidative stress as measured by serum concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Design: Double-blind, randomized, placebo-controlled trial. Setting: University outpatient clinic. Patient(s): The study cohort consisted of 50 obese women (body mass index [BMI] >= 27 kg/m(2)) and 60 nonobese patients (BMI <27 kg/m(2)), mean age was 27.7 +/- 4.0 SD years. Intervention(s): Randomization to receive metformin or placebo for 3 months. Main Outcome Measure(s): Serum levels of 8-OHdG before and after medical treatment. Result(s): The levels of 8-OHdG were equal at baseline in the placebo and metformin groups. Obese women had higher baseline serum concentrations of 8-OHdG. Levels of 8-OHdG were statistically significantly reduced with metformin treatment, especially in obese patients with polycystic ovary syndrome. This study was a secondary subanalysis of a previously conducted prospective multicenter, randomized, placebo-controlled study on the effects of metformin on miscarriage, pregnancy, and miscarriage rates. Conclusion(s): Metformin treatment, compared with placebo, statistically significantly decreased 8-OHdG levels in women with polycystic ovary syndrome. Clinical Trial Registration Number: NCT00994812. (Fertil Steril (R) 2013; 99:593-8. (C) 2013 by American Society for Reproductive Medicine.)