Artificial membrane permeability measurement is a potentially high throughput and low cost alternative for in vitro assessment of drug absorption potential. It will be an ideal screening/profiling tool in the lead generation program of drug discovery research if it is proven to be generally applicable for classifying drug absorption potential and is advantageous over other in vitro or in silico methods. This study provides an in-depth evaluation of the method in close comparison to Caco-2, LogD, LogP, polar surface area (PSA), and quantitative structure-property relationship (QSPR) predictions using a large and diverse compound set. It showed that the accuracy of using artificial membrane permeability in assessing drug absorption is comparable to Caco-2, but significantly better than LogP, LogD, PSA, and QSPR predictions. This study also explored the artificial membrane composition by adopting a hydrophilic filter membrane for artificial membrane (lecithin-dodecane) support. The use of hydrophilic filter membrane increased the rate of permeation significantly and reduced the transport time to 2 h or less as compared with over 10 h when a hydrophobic filter membrane is used.