Inconsistent evidence exists on whether obesity is associated with an increased risk of prostate cancer death post-radical prostatectomy. We examined data from three large health plans to evaluate if an increased body mass index (BMI) at prostate cancer diagnosis is related to prostate cancer mortality This population-based case-control study included 751 men with prostate cancer who underwent radical prostatectomy. Cases were men who died due to prostate cancer (N=323) and matched controls (N=428). We used multivariable logistic regression models to assess the association between BMI at diagnosis and prostate cancer mortality, adjusted for Gleason score, PSA, tumour characteristics, and matching factors. Study subjects were classified into the following BMI (kg/m2) categories: healthy (18.5-24.9), overweight (25-29.9) and obese (?30). Nearly 43% of the participants had a BMI ?25 at diagnosis. A higher fraction of cases (30%) were obese compared to controls (22%). Overall, obese men had more than a 50% increase in prostate cancer mortality (adjusted odds ratio=1.50 [95% CI, 1.03-2.19]) when compared to men with healthy BMI. After stratifying by Gleason score, the odds of mortality generally rose with increasing BMI. The strongest effect was observed in the Gleason score 8+ category (2.37, 95% CI: 1.11-5.09). These associations persisted after adjusting for PSA at diagnosis and other tumour characteristics. These results suggest that BMI at diagnosis is strongly correlated with prostate cancer mortality, and that men with aggressive disease have a markedly greater odds of death if they are overweight or obese.