Skull base surgical approaches have evolved significantly to minimize collateral tissue damage and improve access to complex anatomic regions. Many endoscopic surgical portals have been described, and these can be combined in multiportal approaches that permit improved angles for visualization and instrumentation. To assist in the choice of entry portal and surgical pathway analysis, a three-dimensional computer model with virtual endoscopy was created. The model was evaluated on transnasal and transorbital approaches to access 11 specified sellar and parasellar target locations on 14 computed tomography (CT) scans. Data were collected on length of approach, angle between instruments, and approach angle with respect to anatomical planes. Optimal multiportal approach combinations were derived. The data demonstrated that the shortest, most direct pathway to many sellar and parasellar targets was through transorbital portals. Distances were reduced by 35% for certain target locations; combining transorbital and transnasal portals increased the angle between instruments 4-fold for many targets. The predicted values from the model were validated on four cadaver specimens. Computer modeling holds the potential to play an integral role in the design, analysis, and testing of new surgical approaches, as well as in the selection of optimal approach strategies for the unique pathology of individual patients.