Introduction: We analyzed the biochemical recurrence-free survival (BRFS) of patients with high-risk prostate cancer (HRCaP) as per the D'Amico classification undergoing radical prostatectomy (RP) at our center. We aimed to determine whether the number and type of risk factors (cT2c-T3b, prostate-specific antigen >20 ng/ml, Gleason score >7) are associated with biochemical recurrence (BCR) in HRCaP patients undergoing RP in the Indian population. Methods: Between 2006 and 2017, 192 patients underwent RP (open RP [ORP], laparoscopic RP [LRP], and robotic RP [RRP]) at our center, of which 109 had D'Amico HR disease. Preoperative, postoperative, and pathological outcome data were analyzed for patients with HR disease as per the D'Amico classification. Subgroups were formed to determine whether an increasing number of risk factors (1, 2, or 3) were associated with poorer oncological results and early BCR. The Kaplan–Meier method with log-rank test was used to test the difference in BRFS between the groups. Univariate and multivariate analyses were done to find significant variable against BCR. Results: According to the D'Amico criteria, 109 patients had HR, 63 patients had intermediate-risk, and 19 patients had low-risk disease. These 109 patients with HR disease were analyzed in our study (50 RRP, 33 ORP, and 26 LRP). A total of 59 (54.1%) patients had one HR factor (1HR), 44 (40%) had two HR factors (2HR), and 6 (5.5%) had three HR factors (3HR). The mean follow-up for our patient population was 21.5 ± 19 months (median 18 months; range, 0–108). Overall, the 2-year and 5-year BRFS was 45% and 35%, respectively (mean BRFS 46 ± 6 months). Two-year BRFS was 63%, 23%, and 22%, respectively, for 1HR, 2HR, and 3HR (logrank, P < 0.0001). The prognostic substratification based on the three risk factors was significantly predictive for adverse pathologic features and oncologic outcomes. Conclusion: Substratification based on the three well-defined criteria leads to a better identification of the more aggressive cancers and prediction of need for additional treatment modalities. Localized HRCaP includes a heterogeneous population of patients with variable oncological outcomes.