BACKGROUND: While prism adaptation (PA) has been recognized as a promising tool for treating spatial neglect, implementation as a standard treatment in clinical care has been lagging. Limited evidence for the generalization of after-effects to everyday activities has been a barrier towards implementation. OBJECTIVES: This study examined whether a home-friendly standardized PA protocol (Peg-the-Mole, PTM) induces after-effects that can transfer to wheelchair maneuvering. We also examined the impact of using constant (1 starting hand position) or variable (3 starting hand positions) training conditions on the transfer of after-effects to wheelchair maneuvering. METHODS: Sixty participants were randomly assigned to one of four PTM conditions: 1) prisms/constant training; 2) prisms/variable training; 3) sham goggles/constant training; 4) sham goggles/variable training. RESULTS: The use of PTM with rightward shifting prisms induced after-effects on proprioceptive and visual pointing outcome tasks. Groups using PTM with prism goggles showed a leftward shift in their position within a wheelchair course and a reduction in the number of right-sided collisions. The training condition did not have an impact on the transfer of after-effects to wheelchair driving. CONCLUSION: PTM is a clinically appealing PA protocol that induces after-effects that can transfer to an everyday activity relevant to patients with neglect.