PURPOSE: We report acute patient-reported outcomes using CTCAE (PRO-CTCAE) of proton beam radiotherapy for high-risk or unfavorable intermediate-risk prostate cancer in a prospective clinical trial. PRO-CTCAE were correlated with investigator reported-CTCAE (IR-CTCAE) to assess the degree of concordance. METHODS AND MATERIALS: 11 PRO-CTCAE questions assessed gastrointestinal (GI), genitourinary (GU), or erectile function side effects. The correlation scheme between PRO-CTCAE and IR-CTCAE was independently developed by two physicians. Analyses of PRO-CTCAE and IR-CTCAE were conducted using both descriptive terms and the converted grade scores. The Kappa statistic described the degree of concordance. RESULTS: 55 patients were included. IR-CTCAE underestimated diarrhea compared to PRO-CTCAE at the end of treatment (EOT), with a 28% rate of underestimation (11% by ≥ 2 toxicity grades). Similarly, urinary tract pain was underestimated in 45% of cases (17% by ≥ 2 grades) at EOT. Differences were less pronounced at baseline or 3 months after radiotherapy. The incidence of urinary urgency and frequency tended to be overestimated prior to treatment (36% and 24%, respectively) but underestimated at EOT (35% and 31%, respectively). The degree of interference with daily activities was consistently overestimated by investigators (45%-85%). Finally, erectile dysfunction showed a 36-56% rate of discordance by ≥ 2 toxicity grades. CONCLUSIONS: Our study shows a low agreement between IR-CTCAE and PRO-CTCAE in the setting of proton therapy for prostate cancer. Compared to patient-reported outcomes, physicians underestimated the frequency and severity of urinary symptoms and diarrhea at the end of treatment. Continued use of PROs should be strongly encouraged.