Background: While level one evidence has shown an overall survival (OS) advantage with the addition of androgen deprivation therapy (ADT) to radiotherapy (RT) for intermediate risk prostate cancer (PCa), the benefit in the era of modern dose escalation is controversial, especially given the heterogeneity within this risk group. We assessed the impact of adding ADT to high dose RT on OS for intermediate risk PCa stratified by number of intermediate risk factors (IRF). Methods: We identified 114,339 men with intermediate risk PCa (Gleason 7, clinical stage T1-2, PSA < 20 ng/mL) using the National Cancer Database. Men were stratified into the following subgroups based on the number of IRFs (Gleason 7, cT2b-c, PSA > 10-20 ng/mL): A) Gleason 3+4 and no other IRF, B) Gleason 4+3 and no other IRF, C) two IRFs, and D) three IRFs. The addition of ADT to dose-escalated external beam RT (DE-EBRT, ≥ 75.6 Gy), brachytherapy (BT), or combination EBRT+BT on OS was assessed within each subgroup using Kaplan-Meier and log-rank tests in propensity score-matched cohorts in all men and subsequently only in those with Charlson-Deyo comorbidity index (CDI) of zero. Results: There was no OS benefit with the addition of ADT to DE-EBRT, BT, or EBRT+BT in groups A, B, and C, even after limiting the cohort to men with CDI = 0. However, in group D, the addition of ADT to DE-EBRT was associated with a trend for OS improvement in patients with CDI = 0 only (8-year OS with and without ADT 68.3% and 62.4%, respectively, log-rank P= .07). Conversely, there was a trend for OS decrement with the addition of ADT to DE-EBRT in men with CDI ≥ 1 (8-year OS with and without ADT 61.8% and 67.5%, respectively, log-rank P= .06). There was no OS benefit of ADT in group D treated with BT or EBRT+BT, regardless of comorbidity status. Conclusions: The OS benefit of ADT in men with intermediate risk PCa may be limited to those with 3 IRFs and minimal comorbidities treated with DE-EBRT. If prospectively validated, extreme dose escalation achieved with BT (alone or in combination with EBRT) may obviate the addition of ADT in all men with intermediate risk disease, especially in an era of advanced molecular imaging.