Background Several pharmacologic treatments for hirsutism are used in practice; however, their relative efficacy is unclear. Methods We searched MEDLINE, EMBASE, and CENTRAL through January 2017 for randomized controlled trials (RCTs) with follow-up of at least 6 months that evaluated antiandrogens, insulin sensitizers, and oral contraceptives in women with hirsutism. Independent pairs of reviewers selected and appraised trials. Random-effects network meta-analysis was used to compare individual drugs and classes. Results We included 43 trials. Estrogen-progestin oral contraceptives pills (OCPs), antiandrogens, and insulin sensitizers were superior to placebo, with standardized mean reductions (95% confidence intervals) of -0.94 (-1.49 to -0.38), -1.29 (-1.80 to -0.79), and -0.62 (-1.00 to -0.23), respectively. Antiandrogen monotherapy, the combination of OCP and antiandrogen, the combination of OCPs and insulin sensitizer, and the combination of antiandrogen and insulin sensitizer were superior to insulin sensitizer monotherapy. The combination of OCPs and antiandrogen was superior to OCPs. Antiandrogen monotherapy with flutamide, finasteride, and spironolactone were each superior to placebo but similar to each other in efficacy. OCPs containing levonorgestrel, cyproterone acetate, or drospirenone were similar in effectiveness to other OCPs or had trivial differences. The certainty in comparisons with placebo was moderate and for head-to-head comparisons was low. Conclusions Estrogen-progestin OCPs, antiandrogens, and insulin sensitizers are superior to placebo for the treatment of hirsutism.