Central and perpendicular (PERP) screw orientations have each been described for scaphoid fracture fixation. It is unclear, however, which orientation produces greater compression.  This study compares compression in scaphoid waist fractures with screw fixation in both PERP and pole-to-pole (PTP) configurations. PERP orientation was hypothesized to produce greater compression than PTP orientation.  Ten preoperative computed tomography scans of scaphoid waist fractures were classified by fracture type and orientation in the coronal and sagittal planes. Three-dimensional models of each scaphoid and fracture plane were created. Simulated Acutrak 2 (Acumed, Hillsboro, OR) screws were placed into the models in both PERP and PTP orientations. Engagement length and screw angle relative to the fracture were measured. Compression strength was calculated from the shear area, average density, and angle acuity.  The PTP angle between screw and fracture ranged from 36 to 84 degrees. By definition, the PERP screw-to-fracture angle was 90 degrees. Perpendicularity of the PTP screw to the fracture was positively correlated to compression strength. PERP screws had greater compression than PTP screws when the PTP screw-to-fracture angle was < 80 degrees (106 vs. 80 N), but there was no difference in compression when the PTP screw-to-fracture angle was > 80 degrees, approximating the PERP screw.  Increasing screw perpendicularity resulted in higher compression when the screw-to-fracture angle of the PTP screw was < 80 degrees. Maximum compression was obtained with a screw PERP to the fracture. The increased compression gained from PERP screw placement offsets the decreased engagement length.  These results provide guidelines for optimal screw placement in scaphoid waist fractures.