Flaking-type wear, so-called delamination, is often observed in polyethylene joint components. This is thought to occur partly due to crack formation and propagation at grain boundaries. This study examined the effect of vitamin E on the crack formation and/or propagation in UHMWPE by using 2-dimensional sliding fatigue testing and micro indenter testing. An in vitro sliding fatigue test was performed under two simplified articulating movements, and the cracks produced were observed by scanning acoustic tomography (SAT). Gamma-irradiated ultrahigh molecular weight polyethylene (UHMWPE) specimens demonstrated a smaller area of accumulated cracks as compared to virgin specimens, when the loading movement was reciprocated on a single linear locus. However, four out of five gamma-irradiated UHMWPE specimens exhibited severe flaking-like destruction under the complicated sliding condition, suggesting that gamma irradiation accelerated crack propagation under multidirectional loading. All the gamma-irradiated vitamin-E-containing specimens demonstrated no subsurface crack formation and no flaking-like destruction. Results using micro indenter testing showed that the dynamic hardness at grain boundary was higher than that in grain, and was increased by gamma irradiation. This hardening at grain boundary was reduced by adding vitamin E. It is possible that the presence of vitamin E prevents crack propagation partly due to reduced hardness at grain boundaries. The gamma-irradiated vitamin-E-containing UHMWPE is a promising material to prevent flaking-like destruction of polyethylene joint components.