BACKGROUND This research explored the role of attitudes in acceptance of organizational change initiatives. METHODS A survey assessed factors associated with health care provider (HCP) likelihood to accept seasonal influenza vaccine policy changes. We evaluated the impact of knowledge and individual attitudes on this outcome measure. RESULTS Knowledge of seasonal influenza vaccine and influenza recommendations was a significant predictor of HCP's attitudes toward vaccine at the individual (p<0.001), organizational (p<0.05), and legislative level (p<0.05). Mixed results were obtained when investigating the impact of knowledge on actual willingness to accept vaccine, suggesting that knowledge was only a significant predictor at the organizational (p<0.05) and legislative levels (p<0.05). Attitudes fully mediated the impact of knowledge at both the organizational and legislative levels. INTERPRETATION Knowledge of seasonal influenza and vaccine recommendations is an important, but insufficient predictor of willingness to accept policy change.