Calcium methoxide catalyst was synthesized from quick lime and methanol, and further characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and energy dispersive X-ray spectroscopy (EDX). Response surface methodology (RSM) with a 5-level-3-factor central composite was applied for the calcium methoxide catalyzed transesterification of refined palm oil to investigate the effect of experimental factors on the methyl ester yield. A quadratic model with an analysis of variance (ANOVA) obtained from RSM is suggested for the prediction of methyl ester yield, and reveals that 95.99% of the observed variation is explained by the model. The optimum conditions obtained from RSM were 2.71 wt% of catalyst concentration, 11.5 : 1 methanol-to-oil molar ratio, and 175 min of reaction time. Under these conditions, the produced biodiesel met the standard requirements for methyl ester yield.