Objective To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC). Materials and Methods Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared. Results Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P =.8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P =.2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6). Conclusion In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC.