Background: In international guidelines, target volumes for postoperative radiotherapy (PORT) after radical prostatectomy concern the bed of the prostate and seminal vesicles. The benefit of whole pelvic nodal radiotherapy (WPRT) in the case of PORT remains uncertain. Methods: We reviewed the charts of all patients diagnosed with high-risk prostate cancer after radical prostatectomy who were selected for PORT and treated with adjuvant radiotherapy (n = 242, 43.1%) or early salvage RT (n = 320, 56.9%) between 2002 and 2011. 111 patients (19.8%) who underwent WPRT were compared with 441 patients (80.2%) who had prostate bed radiotherapy only (PBRT). We examined associations between patient, tumor, and treatment characteristics and biochemical progression-free survival (bPFS), disease-free survival (DFS) and overall survival (OS) with uni- and multivariate analyses using Cox models. Acute and late toxicities were also compared between the two groups. Results: We found a significantly lower rate of acute G2+ gastrointestinal (GI) toxicity with PBRT than with WPRT with neither difference in acute G3+ nor on late GI toxicity. Regarding genitoruinary (GU) toxicity, we found no difference in acute G2+ or G3+ toxicity but rates of late G3+ GU toxicity were significantly lower in PBRT (1.55%) than in WPRT patients (p = 0.035). With a median follow-up of 65.2 months [95% CI: 62.8 - 67.9], a deleterious effect of WPRT was observed on OS (HR = 3.27 [95% CI: 1.44 - 7.45], p = 0.009). We found no impact of WPRT on bPFS (HR = 0.79 [95% CI: 0.49 - 1.25], p = 0.31) or DFS (HR = 0.97 [95% CI: 0.63 - 1.49], p = 0.88). Only a positive surgical margin was an independent prognostic factor for better bPFS. Age≥63 years and WPRT (HR = 2.86 [95% CI: 1.20-6.80], p = 0.018) were independent prognostic factors for worse OS. Conclusions: After radical prostatectomy, we found no difference on bPFS or DFS but lower rates of OS with WPRT compared to PBRT. PBRT must remain the standard of care. The results of RTOG NRG Oncology 0534 should shed light on this unresolved issue.