Purpose: Calibration of a radiotherapy electronic portal imaging device (EPID) using the pixel-sensitivity-map (PSM) in place of the flood field correction improves the utility of the EPID for quality assurance applications. Multiple methods are available for determining the PSM and this study provides an evaluation to inform on which is superior. Methods: Three different empirical methods (“Calvary Mater Newcastle” [CMN], “Varian,” and “WashU”) and a Monte Carlo-based method of PSM determination were investigated on a single Varian TrueBeam STx linear accelerator (linac) with an aS1200 EPID panel. PSM measurements were performed for each empirical method three successive times using the 6 MV beam. The resulting PSM from each method was compared to the Monte Carlo method as a reference using 2D percentage deviation maps and histograms plus crossplane profiles. The repeatability of generated PSMs was also assessed via 2D standard deviation (SD) maps and histograms. Additiona