The degradation test of direct methanol fuel cells (DMFCs) under on-off operation with variable load profile, known as a variable load on-off operation (VLOO) mode, was compared to continuous operation with a constant load, known as a constant load continuous operation (CLCO) mode. It was found that the performance loss in the VLOO mode was higher than that under the CLCO mode in terms of open circuit voltage drop (3.6 times higher) and the maximum power density reduction rate (1.23 times greater). Under both operation modes, the anode catalyst was deteriorated by Ru dissolution. However, the faster decay of cell performance under VLOO mode was mainly caused by the increase of cathode polarization due to higher methanol crossover and the decrease of Pt activity to the oxygen reduction reaction induced by Ru deposition. Copyright (C) 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.