50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI<25 kg/m2), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI >40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p<0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p<0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment.