Abiraterone acetate combined with prednisone improves survival in metastatic castration-resistant prostate cancer (mCRPC) patients. This oral anticancer agent may result in drug-drug interactions (DDI). We aimed to evaluate the prevalence of DDI with abiraterone and the possible determinants for the occurrence of these DDI. We performed a single centre retrospective review from electronic medical records of mCRPC patients treated with abiraterone from 2011 to 2015. Potential DDI with abiraterone were identified using Micromedex and were categorized by a 4-point scale severity. Seventy-two out of ninety-five mCRPC pts (median age: 77 years [68-82]) had comorbidities. The median number of drugs used per patient was 7 [5-9]. 66 potential DDI with abiraterone were detected in 49 patients (52%): 39 and 61% were classified as major and moderate DDI, respectively. In the univariate analysis, pain (p < 0.0001), hypo-albuminemia (p = 0.032), and higher ECOG performance status (PS) (p = 0.013) were significantly associated with a higher risk of DDI with abiraterone. Pain (p < 0.0001) and PS (p = 0.018) remained significant in the multivariate analysis. Polypharmacy is an issue among mCRPC patients. In our study, half of the patients have potential DDI with abiraterone. Patients with pain and poor PS are at higher risk of DDI with abiraterone. A medication review by a pharmacist is of crucial importance to prevent DDI with abiraterone.