The suitability of grafted vitamin-E highly crosslinked polyethylene (VE-HXPE) for use in posterior stabilized (PS) and constrained condylar knee (CCK) applications has not been explored. We hypothesized that VE-HXPE performs better than conventional and crosslinked polyethylene under clinically relevant conditions. PS tibial post fracture resistance under adverse shear loading conditions, CCK tibial post resistance to torsional fatigue, delamination resistance under high stress, and wear resistance were evaluated. Grafted VE-HXPE exhibits (1) 10% and 57% improved PS post fatigue strength compared to conventional PE (CPE) and remelted HXPE; (2) 45% improved CCK post fatigue strength compared to CPE; (3) Greater than 36× the delamination resistance of CPE; and (4) 96% and 73% wear reduction compared to CPE and HXPE. VE-HXPE performed well under clinically relevant in vitro conditions. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1789-1798, 2017.