Purpose/Objective(s): The objective of this study was to evaluate factors related to patients’ health (age, performance status, comorbid illnesses, smoking history), patients’ prostate cancer (Gleason score (GS), prostatespecific antigen (PSA), clinical T stage), and patients’ radiation (radiation therapy (RT) dose, RT fields, use of concurrent hormone therapy (HT)) in order to determine which factors most contribute to mortality. Materials/Methods: From 2000-2009, 211 patients diagnosed with intermediate-risk prostate cancer were treated with external beam RT (EBRT) at our institution. Each patient’s comorbid medical illnesses were scored according to the Charlson Comorbidity Index. Tobacco use was assessed based on total pack-yr history and use at the time of RT. The Karnofsky Performance Status (KPS) was determined at the time of initial consultation. Each patient was classified as having IR disease using NCCN criteria base on GS, PSA, and T stage. All patients were treated with definitive EBRT and the dose, field, and use of HT varied over time. Results: In this population, the mean age was 66 (range: 50-83). The patients had average KPS of 93.5 (range: 40-100). The average Charlson Comorbidity score (CCS) was 1.47 (range: 0-6). The average number of pack-yrs of smoking was 32.6 (range: 0-141). The median RT dose was 70.2 Gy (range: 62.8-79.2) and 70.2 Gy was also the mode. Whole pelvic RT fields were used in 35.4% and 24.6% received HT. The biochemicalfree survival (BCFS) was 86.4% at 5 yrs and 70.0% at 10 yrs with a median time to failure of 4.2 yrs. There was no statistically significant difference in BCFS when stratified by T stage, GS, or PSA. No statistical significance was found when stratified by RT dose, RT field, or use of HT. With a median survival of 11.8 yrs, the 5-yr and 10-yr overall survival (OS) were 83.3% and 59.6%, respectively. Patients with a KPS >80 had a 10-yr OS of 65.7% compared to 32.0% with worse KPS (p Z 0.006). A CCS of 2 correlated to a 10-yr OS of 61.4% compared to 51.7% with higher CCS (pZ 0.048). Patients with <10 pack-yr smoking history had a 10-yr OS of 75.7%% compared to 56.9% for those who smoked more (p Z 0.039). There was no statistically significant difference in OS when stratified by T stage, GS, PSA, RT dose, RT field, or HT. On multivariate analysis only KPS <80 and 10 pack-yr smoking history were statistically significant with relative risk of 2.08 (1.1-3.8) and 2.4 (1.0-5.6), respectively. The disease-specific survival was 98% at both 5 yrs and 10 yrs. Of 59 deaths in the study, only 3 were from prostate cancer. Other causes of death were cardiopulmonary in 19 (32.2%), other malignancy in 12 (20.3%), other/ unknown in 24 (40.7%). One patient died from radiation proctitis. Conclusions: The greatest determinants of survival in intermediate-risk prostate cancer are patient elated factors of performance status, comorbid illnesses, and smoking history and not cancer or treatment related factors. Author Disclosure: J.R. Bagley: None. D. Lindsay: None. P. Tripp: None. S. Firat: None.