The efficacy of ultrasonication pretreatment method for complex food waste prior to anaerobic digestion is evaluated for enhancement of H-2 yield (HY) and rate (R). The RSM results showed that the ultimate H2 production increased with increasing TS content and ultrasonication time (UT). Desirability function integrated with RSM predicted an optimum condition of TS and UT as: 8% TS and 12 min, for maximization of HY and R. The highest HY, 149 mL/g VSadded, and R, 5.23 mL/h, were achieved during the verification test at optimized conditions. Furthermore, a significant decreased lag phase followed by highest molar HBu/HAc ratio (2.2) was also achieved at optimized conditions with lowest specific energy input (13,500 kJ/kg TS). The significant relative enhancement of HY, 75%, and R, 104%, implies that ultrasonically pretreated complex food waste with higher TS loading is about 1.7-2.1 times more effective for enhanced bioH(2) production compared to unsonicated food waste. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.