Purpose: To analyze outcomes and complication rates in an unselected cohort of men with unfavorable (NCCN intermediate and high-risk) PCa receiving combined-modality radiation treatment (CRT). Methods: Patients received androgen deprivation therapy for 1 year and combined-modality radiation treatment (CRT) consisting of external-beam radiotherapy (EBRT, 59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Subgroups, including WHO group 3–5, and initial PSA (iPSA) < 20 and > 20 ng/ml were identified. Biochemical recurrence-free (BRFS), metastasis-free (MFS), cancer-specific (CSS) and overall survival (OS) were calculated at 5 and 10 years using the Kaplan–Meier method. Subgroups were compared using log-rank test and Cox proportional hazards regression. Urogenital and gastrointestinal side-effects were reported according to the CTCAE classification. Results: After a median of 6.9 years (range 2–13) calculated 5- and 10-year rates for the whole cohort of 425 men were 92.8% and 82.5% for BRFS, 95.1%, and 88.8% for MFS, 98.2%, and 95.1 for CSS, and 95.4%, and 80.1% for OS, respectively. Univariate (UVA) and multivariate analysis (MV) identified a group with unfavorable outcome with iPSA > 20 ng/ml, comprising 24% of all patients, in which 55% of recurrences, 54% of metastases and 71% of cancer-specific deaths occurred. Side-effects were limited, with < 5% of patients complaining of genitourinary and 0.5% of gastrointestinal AEs after 5 years. Conclusion: CRT is an excellent treatment option for men with unfavorable PCa. In a subgroup of patients with iPSA > 20 ng/ml further, possibly systemic, treatment options should be identified.