Background: Second generation androgen receptor signaling inhibitors such as A and E are commonly used first-line treatment options for mCRPC. While differences in the side effect profile of these agents are well documented, there are no predictive markers of response to A versus E, and there is a paucity of comparative outcome data. Methods: We conducted a retrospective exploratory analysis of 100 mCRPC patients (pts) treated at Odette Cancer Centre (Toronto, ON, Canada) between August 2012 and June 2020 with either A (n = 50) or E (n = 50). Pts undergoing first-line mCRPC therapy were randomly selected from a list of 327 A and 254 E patients. Following extraction of disease and pt characteristics, as well as outcome data, we applied the Wilcoxon rank-sum nonparametric test or the Fisher exact test for continuous or categorical variables, respectively, for between group comparisons. For time to event analyses, we created Kaplan-Meier (KM) curves with log-rank testing. Two-sided p-values < 0.05 were considered significant. Results: The A and E cohorts were comparable regarding diagnostic PSA, Gleason score categories, and treatments prior to presentation with mCRPC. The median time to CRPC in the A cohort was 23.3 (95%CI 15.6-29.9) months, compared to 24.1 (19.4-37.4) months in the E cohort (p = 0.942). At initiation of A or E therapy both the median (Q1,Q3) age (77(70,82) vs 76(69,81) years) and median Charlson Comorbidity Index (10(9,11) vs 10(9,11)) were similar (p = 0.469 and p = 0.736, respectively). The rate of diabetes was significantly lower in the A group (8% vs 38%; p < 0.001), but there were no significant differences in cardiovascular comorbidities. Pts starting A therapy had a higher rate of bone metastasis (92% vs 68%; p = 0.005); otherwise, the metastatic pattern did not differ. The median PSA at start of A was 46.75 (13.77,176.80), compared to 27.07 (8.64,136.20) in the E group (p = 0.218). Baseline ALP, hemoglobin and albumin were all comparable. Median follow-up was 13.7 (8.3,26.3) and 19.5 (9.8,34.0) months in the A and E groups (p = 0.091). 38% of A pts and 44% of E pts went on to further lines of systemic therapy upon progression (p = 0.685). The median time to next line of systemic therapy was 11.3 (95%CI 8.3-15.9) months for the A cohort and 12.7 (9.7-16.6) for the E cohort (p = 0.844). The actuarial median overall survival from KM estimations was 35.7 (20.4-52.5) months for the A group, and 34.0 (25.7-38.0) months for the E group. Conclusions: In men undergoing first-line A or E therapy for mCRPC, time to next line of systemic therapy and overall survival did not differ significantly, while baseline pt and disease characteristics were largely similar. A substantial number of pts do not receive ≥2 lines of therapy for mCRPC under real-world circumstances.