Few anabolic-androgenic steroid (AAS) users disclose their performance enhancing drug (PED) use with their healthcare providers. AAS users practice polypharmacy with prescription medications to counter adverse effects of AAS, to further their muscular gains, or to lose weight.To compare and contrast AAS using and non-AAS using gym clients regarding PED use, in particular prescription drugs.The CASTRO (Castro Anabolic Steroid Research Observation) study was a 108-item cross-sectional survey that took place at four gyms in San Francisco, California between August 2015 and January 2016. 40 AAS users and 179 non-AAS users completed the survey.The prevalence of AAS use in the study cohort was 18.3%. AAS users reported using a greater number of total PEDs (8.7 ± 4.2 vs. 3.7 ± 2.1, p < 0.001) than non-AAS users. AAS users were more likely to misuse the following prescription drugs: antiestrogens (tamoxifen, anastrazole), fertility agents (clomiphene, human chorionic gonadotropin), erectile dysfunction drugs (tadalafil, sildenafil), anabolic drugs (clenbuterol, recombinant human growth hormone), and weight loss drugs (liothyronine).AAS users practice polypharmacy and misuse multiple prescription drugs. These findings allow researchers and clinicians to be more knowledgeable and to anticipate potential misuse of prescription medications that traditionally are not thought to be abused.