We evaluated the production of bioH2 from Cassava Processing Wastewater (CPW) using three microbial consortia (Vac, Esg, and Lod) from different Brazilian environments. These consortia consisted of bacteria of the genera Clostridium, Sporanaerobacter, Coprococcus, Enterococcus, and others. The CPW was supplemented with nitrogen and used raw or hydrolyzed and sterilized or not. Four independent variables were optimized (Box-Behnken design): pH, temperature, C/N ratio, and inoculum ratio. Three quadratic models were obtained and explain production of bioH2 (R2 of 0.93, 0.87 and 0.82 for the consortia Vac, Esg and Lod, respectively). The quadratic effects were the most significant in comparison to linear effects and interactions. The optimal conditions were: pH: 5.5–7.0; temperature 37-39 °C; inoculum ratio 15%, and C/N ratio 5-3,5. After 48 h, the maximum yields of hydrogen obtained with hydrolyzed and sterilized CPW were 1.82, 1.7 and 1.68 mols of H2/mol of maltose for Lod, Esg and Vac, respectively. While, for the only sterilized substrate the yields are in the range 1.33–1.54 mol H2/mol maltose.