OBJECTIVE To investigate the potential benefits achievable with biological optimization for modulated volumetric arc (VMAT) treatments of prostate carcinoma. METHODS Fifteen prostate patient plans were studied retrospectively. For each case, planning target volume, rectum, and bladder were considered. Three optimization schemes were used: dose-volume histogram (DVH) based, generalized equivalent uniform dose (gEUD) based, and mixed DVH/gEUD based. For each scheme, a single or dual 6-MV, 356° VMAT arc was used. The plans were optimized with Pinnacle(3) (v. 9.0 beta) treatment planning system. For each patient, the optimized dose distributions were normalized to deliver the same prescription dose. The quality of the plans was evaluated by dose indices (DIs) and gEUDs for rectum and bladder. The tallied DIs were D(1%), D(15%), D(25%), and D(40%), and the tallied gEUDs were for a values of 1 and 6. Statistical tests were used to quantify the magnitude and the significance of the observed differences. Monitor units and treatment times for each optimization scheme were also assessed. RESULTS All optimization schemes generated clinically acceptable plans. The statistical tests indicated that biological optimization yielded increased organs-at-risk sparing, ranging from ~1% to more than ~27% depending on the tallied DI, gEUD, and anatomical structure. The increased sparing was at the expense of longer treatment times and increased number of monitor units. CONCLUSIONS Biological optimization can significantly increase the organs-at-risk sparing in VMAT optimization for prostate carcinoma. In some particular cases, however, the DVH-based optimization resulted in superior treatment plans.