Adjuvant androgen deprivation therapy (ADT) improves outcomes of patients receiving definitive radiotherapy (RT) for local-regionally advanced prostate cancer. However, patients in most randomized trials had more advanced disease than observed in many practices and were treated with suboptimal RT doses. Although data are conflicting, long-term ADT likely has adverse side-effects in patients with comorbidities. We recommend 6 months of ADT monotherapy with gonadotropin-releasing hormone agonist and RT for patients with high-risk prostate cancer (≥T2c, Gleason Score 8 to 10, and/or prostate-specific antigen ≥20 ng/mL) with minimal or no comorbidities. Adjuvant ADT for unfavorable intermediate-risk patients with a Gleason Score of 4+3=7 is also reasonable.