Orange peels were evaluated as a fermentation feedstock, and process conditions for enhanced ethanol production were determined. Primary hydrolysis of orange peel powder (OPP) was carried out at acid concentrations from 0 to 1.0% (w/v) at 121 degrees C and 15 psi for 15 min. High-performance liquid chromatography analysis of sugars and inhibitory compounds showed a higher production of hydroxymethyfurfural and acetic acid and a decrease in sugar concentration when the acid level was beyond 0.5% (w/v). Secondary hydrolysis of pretreated biomass obtained from primary hydrolysis was carried out at 0.5% (w/v) acid. Response surface methodology using three factors and a two-level central composite design was employed to optimize the effect of pH, temperature, and fermentation time on ethanol production from OPP hydrolysate at the shake flask level. On the basis of results obtained from the optimization experiment and numerical optimization software, a validation study was carried out in a 2 L batch fermenter at pH 5.4 and a temperature of 34 degrees C for 15 h. The hydrolysate obtained from primary and secondary hydrolysis processes was fermented separately employing parameters optimized through RSM. Ethanol yields of 0.25 g/g on a biomass basis (YP/X) and 0.46 g/g on a substrate-consumed basis (YP/S) and a promising volumetric ethanol productivity of 3.37 g/L/h were attained using this process at the fermenter level, which shows promise for further scale-up studies.