Previous research demonstrates that high-involvement work practices (HIWPs) may be associated with burnout (emotional exhaustion and depersonalization); however, to date, the process through which HIWPs influence burnout is not clear. This article examined the impact of HIWPs on long-term burnout (emotional exhaustion and depersonalization) by considering the mediating role of person-organization fit (P-O fit) in this relationship. The study used a time-lagged design and was conducted in a Canadian general hospital among health care personnel. Findings from structural equation modeling (N = 185) revealed that perceived HIWPs were positively associated with P-O fit. There was no direct effect of HIWPs on burnout; rather, P-O fit fully mediated the relationship between employee perceptions of HIWPs and burnout. This study fills a void in the HR and burnout literature by demonstrating the role that P-O fit has in explaining how HIWPs alleviate emotional exhaustion and depersonalization. © 2016 Wiley Periodicals, Inc.