The literature contains conflicting data on preoperative predictors of estimated blood loss (EBL) at radical retropubic prostatectomy (RRP). We sought to examine preoperative predictors of EBL at the time of RRP among patients from the SEARCH database to lend clarity to this issue. A total of 1154 patients were identified in the SEARCH database who underwent RRP between 1988 and 2008 and had EBL data available. We examined multiple preoperative factors for their ability to predict EBL using multivariate linear regression analysis. Median EBL was 900 ml (s.d. 1032). The 25th and 75th percentile for EBL were 600 and 1500 ml, respectively. EBL increased significantly with increasing body mass index (BMI) and increasing prostate size and decreased with more recent year of RRP (all P<0.001). The mean-adjusted EBL in normal-weight men (BMI<25 kg/m(2)) was 807 ml compared to 1067 ml among severely obese men (BM I>or=35 kg/m(2)). Predicted EBL for men with the smallest prostates (<20 g) was 721 ml, compared to 1326 ml for men with prostates >or=100 g. Finally, statistically significant differences between centers were observed, with mean-adjusted EBL ranging from 844 to 1094 ml. Both BMI and prostate size are predictors of increased EBL. Prostate size is of particular note, as a nearly twofold increased EBL was seen from the smallest (<20 g) to the largest prostates (>or=100 g). Over time, average EBL significantly decreased. Finally, significant differences in EBL were observed between centers. Patients with multiple risk factors should be forewarned they are at increased risk for higher EBL, which may translate into a greater need for blood transfusion.