In this study, the performance of the Purolite A503S anion exchange resin as a heterogeneous catalyst in the transesterification reaction of palm olein (Elaeis guineensis Jacq.) for ethyl biodiesel production was investigated, and the independent variables were optimized based on the maximum conversion to fatty acid ethyl esters. The response surface methodology (RSM) coupled to a factorial design (2³) with a central composite rotatable design (CCRD) was used for optimization. The effects of temperature, catalyst percentage, palm olein:ethanol molar ratio, and their interactions were evaluated. A reaction time of 10 h was established relating conversion versus time, and the stirring speed was determined by assessing the conversion potential ranging from 250 to 1000 rpm. The reactions were performed in a jacketed reactor coupled to a thermostatic bath. The mixtures of triacylglycerols (TAG), diacylglycerols (DAG), monoacylglycerols (MAG), fatty acid ethyl esters (FAEE), and ethanol were quantified by high-pressure size exclusion chromatography (HPSEC), and glycerol content was determined by stoichiometry. A second-order model was adjusted to explain the experimental data from the 18 factorial design trials. A conversion of approximately 98.10 % in ethyl esters was obtained from the optimised variables using a 17.6 % catalyst, palm olein:ethanol molar ratio of 1:12.85 at 49.4 °C. Despite the long reaction time, the Purolite A503S resin is a potential heterogeneous catalyst in transesterification reactions.