This study systematically investigated the anaerobic digestibility of durian shell and focused on maximizing the methane yield using response surface methodology. Results showed in the feedstock to inoculum (F/I) ratio range of 0.2-2, a lower value was preferred. Meanwhile the methane yield showed a sharp rise first followed by a decline as the organic loading (OL) increased from 3 to 27 g VS/L. The highest experimental methane yield (EMY) was calculated to be 170.6 ml/g VS at F/I ratio of 0.2 and organic loading of 20.45 g VS/L. To make the combination of F/I ratio and OL more practical, 0.5 was set as the optimum F/I ratio, when the highest EMY was obtained to be 165.0 ml/g VS at the OL of 20.45 g VS/L. Characteristics of final effluent implied the anaerobic system was stable. This study is important to promote the application of durian shell into anaerobic digestion from theory to practice. (C) 2017 Published by Elsevier Ltd.