This study was performed to optimize thermal hydrolysis pretreatment (THP) of sewage sludge for enhanced anaerobic digestion (AD). Using the response surface methodology (RSM), the optimal conditions were found 180 degrees C of reaction temperature and 76 min of reaction time. Through THP under optimal conditions, high molecular substances in sewage sludge such as soluble microbial by-products (SMPs) and extracellular polymeric substances (EPSs) were hydrolyzed into low molecular ones without the generation of refractory compounds. The microbial community analysis revealed that relative abundances of Methanomicrobia such as Methanosarcina, Methanosaeta (acetoclastic methanogens), and Methanoculleus (hydrogenotrophic methanogens) in AD with THP were higher than those in conventional AD.