Background: Estimations are that 8-18% of newly diagnosed cancer patients have Type 2 Diabetes Mellitus (T2DM). Current guidelines offer no clarification on the choice of therapy for prostate cancer (PCa) patients with T2DM. Since the comorbid PCa—T2DM population is increasing and these patients face unique challenges from adverse events requiring acute care utilization (ACU) it is important to ascertain which medication poses less of a threat of adverse events. The objective of this study was to describe the SEER-Medicare T2DM-PCa population in terms of those with and without complications and determine if T2DM influences ACU and PCa medication choice. Methods: We identified men with primary PCa treated with abiraterone (ABI, 2011) or enzalutamide (ENZ, 2012) with comorbid T2DM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (1999-2019). Patients with a missing date of diagnosis, those diagnosed at death, having HMO or no continuous A and B coverage 12 months before diagnosis and 6 months continuous part D coverage before starting treatment as well as 6 months following treatment or until death were excluded. T2DM was identified using ICD-9 and ICD-10 codes. ACU was calculated utilizing the CMS Research Data Assistance Center definition focusing on emergency room visits resulting in in-patent hospitalization during the 6 months following treatment initiation. Differences in emergency room in-patient visits were evaluated using negative binomial models adjusted for age, race, SEER region, marital status, state-buyin, education, income, and modified Charlson Comorbidity Index (excluding T2DM). Results: The sample of 11,163 men included 61.8% treated with ABI and 38.2% with ENZ. We identified 3,044 (27.3%) men with T2DM, of which, 59.1% were treated with ABI and 40.8% with ENZ. Compared to those without T2DM those with T2DM had more ACU, regardless of medication, with a higher rate in the ABI than ENZ group, see table. Among diabetics, those with complications related to T2DM compared to those without also experienced a higher rate of ACU. The rate of ACU was 43% higher among those treated with ABI compared to ENZ (IRR 1.43; 95% CI 1.28, 1.61). Overall mortality (15.7% vs 10.1%, p<0.01) and PCa-specific mortality (8.2% vs 5.3%, p<0.01) were worse in those with T2DM treated with ABI compared to ENZ. Conclusions: Outcomes for PCA patients with T2DM are worse than for those without. ACU is higher in men treated with ABI compared to ENZ regardless of T2DM status. Given the worse outcomes for comorbid T2DM patients, further study to evaluate comorbidity management in this population is warranted.