Background: While ARSIs have become a cornerstone in treatment for prostate cancer, nonadherence to these oral medications is common. We investigated the association between patterns of prior nonadherence to medications for chronic conditions with ARSI nonadherence. Methods: In this retrospective cohort study, the MarketScan database was searched for patients >18 years old with a prostate cancer claim between 1/1/2014 and 12/31/2019 and who filled >2 ARSI prescriptions between 9/1/2013 and 12/31/2020. Nonadherence to medications for 4 chronic conditions (hypertension, hyperlipidemia, diabetes, benign prostatic hypertrophy (BPH)) in the 12 months before diagnosis was defined as a medication possession ratio (MPR) <80%. Nonadherence to ARSIs was defined as an MPR <80% between the first and last ARSI prescription up to 1 year. We used logistic regression to examine the relationship between nonadherence to prior medications and nonadherence to ARSIs. Results: Among 4,898 patients, 967 (19.7%) were nonadherent to ARSIs. Regarding prior medication nonadherence, of the patients prescribed hypertension medications (n=2602), 15.4% (n=402) were nonadherent to hypertension medications, of those prescribed hyperlipidemia medications (n=2234), 18.8% (n=419) were nonadherent to hyperlipidemia medications, of those prescribed diabetes mediations (n=826), 19.1% (n=158) were nonadherent to diabetes mediations, and of those prescribed BPH medications (n=1827), 13.4% (n=245) were nonadherent to BPH medications. Among those without prior medications (n=1031 [21.1%]), 21.3% of patients were nonadherent to ARSIs. Compared to those without prior medications, those who used at least 1 medication prior to ARSI and were adherent to all of them (n=2919 [59.6%]) had a 17.2% nonadherence rate to ARSI treatment (OR: 0.77; 95% CI: 0.64, 0.91; p: 0.003). Those who used at least 1 medication prior to ARSI and were nonadherent to 1 of them (n=722 [14.7%]) had a 24.0% nonadherence rate to ARSI (OR: 1.16; 95% CI: 0.93,1.46; p: 0.195), while those who used at least 1 medication prior to ARSI and were nonadherent to >2 (n=226 [4.6%]) had a 30.5% nonadherence rate to ARSI (OR: 1.62; 95% CI: 1.18,2.23; p: 0.003). Conclusions: Nonadherence to medications for chronic conditions prior to ARSI treatment is common and associated with greater nonadherence to ARSIs in patients with prostate cancer. History of medication nonadherence could serve a marker to target a high-risk population for adherence interventions.