This study employed the risk perception attitude (RPA) framework to determine whether health care personnel (HCP) influenza-related risk perceptions and efficacy beliefs could be used to segment individuals into meaningful groups related to vaccination uptake, absenteeism, and patient safety beliefs. After pilot interviews, a questionnaire was administered to 318 hospital-based HCP (80%) andnonclinical support staff (20%) in Lexington, KY, in 2011. Follow-up interviews were conducted with 29 respondents. Cluster analysis was used to create 4 groups that correspond to the RPA framework: responsive (high risk, strong efficacy), avoidance (high risk, weak efficacy), proactive (low risk, strong efficacy), and indifference (low risk, weak efficacy). A significant association was found between membership in 1 or more of the 4 RPA groups and the 3 study variables of interest: influenza vaccination uptake (F7,299=2.51, P<.05), influenza-related absenteeism (F7,269=3.6, P<.001), and perceptions of patient safety climate (F7,304=6.21, P<.001). A subset of respondents indicated the principal reasons for not getting vaccinated were "had one before and got sick anyway," "concerned about vaccine safety," and "no convenient time." In follow-up interviews, HCP indicated that employee vaccinations were altruistic, increased herd immunity, and important for patient safety. The RPA framework is a valid health promotion tool for improving patient safety, targeting specific groups for interventions, and improving HCP influenza vaccination rates.