This study investigates biodiesel transesterification optimisation derived from refined palm oil with CaO catalyst combined with 6/2 pulse ultrasonic waves under a vacuum condition. Response surface methodology (RSM) and CCD experiments were applied to achieve optimised conditions of variables i.e.: molar ratio, catalyst loading, ultrasonic intensity (W/g) and reaction time. Based on the results, the highest predicted yield of 96.12% was obtained at the optimum conditions of a molar ratio of 9.69:1, catalyst loading of 8.77%, ultrasonic intensity of 4.60 W/g and 43.03 min reaction time. The agreement between the RSM and experimental results was showed by 92.78% of R-2 and less than 0.05 of P-Value. However, to simplify the preparation process, a molar ratio of 9:1, 8% catalyst loading, 4.67 W/g ultrasonic intensity and 37 min reaction time was tested. It was found that the highest tested yield of 95% was obtained which was slightly less than the optimum condition but with a shorter reaction time. This can lead to a 12.3% energy saving during the process compared with optimum conditions. In addition, the result revealed that pulse sonication gave a better yield and less reaction time for the same ultrasonic intensity compared with others' research.