An urgent need exists for predictive biomarkers that can be sampled noninvasively in men with prostate cancer. Towards this goal, an analysis of androgen receptor (AR) gene status was conducted using plasma DNA samples from androgen-deprivation therapy (ADT)-naive patients receiving ADT with either abiraterone or enzalutamide as part of one of three clinical trials. Statistically significant associations between both gain in AR copy number, or the presence of one of several AR mutations and inferior overall survival and progression-free survival outcomes were observed, relative to those of patients with wild-type AR. Peripheral blood samples were taken within 30 days of initiation of treatment and, therefore, most likely reflect pre-existing genetic alterations, rather than the effects of treatment. These findings indicate that AR-mutation status in plasma DNA samples can be monitored to predict treatment outcomes.