This study presents a novel application of simultaneous microwave and ultrasound (MW/US) irradiations on transesterification of waste vegetable oil. Experiments were conducted in three phases to evaluate: (1) the effect of process parameters on the transesterification reaction mediated by simultaneous MW/US irradiations at a fixed power output rate; (2) the individual and synergistic effects of the two technologies (by changing the power output rates); and (3) the synergistic effect on the power density (by changing the sample volume for a fixed MW/US power output). From the process parametric optimization study, the following conditions were determined as optimum: 6:1 methanol to oil ratio, 0.75% sodium hydroxide catalyst by wt.%, and 2 min of reaction time at a combined power output rate of 200 W(100/100 MW/US). The biodiesel yields were higher for the simultaneous MW/US mediated reactions (similar to 98%) when compared to MW (87.1%) or US (89.8%) irradiations individually. The power density tests revealed that an optimum power output rate must be determined for energy-efficient biodiesel production. This study concludes that the combined irradiations result in a synergistic effect that enhances the biodiesel process performance and yields significantly. Identification of optimal parameters and hindrances concerning both techniques will further allow for large-scale application of the combined technology for biodiesel production. (C) 2014 Elsevier Ltd. All rights reserved.