Background: 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. Methods: After pilot interviews, a questionnaire was administered to 318 hospital-based HCP (80%) and nonclinical support staff (20%) in Lexington, KY, in 2011. Follow-up interviews were conducted with 29 respondents. Results: 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 (F-7,F-299 = 2.51, P < .05), influenza-related absenteeism (F-7,F-269 = 3.6, P < .001), and perceptions of patient safety climate (F-7,F-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. Conclusion: The RPA framework is a valid health promotion tool for improving patient safety, targeting specific groups for interventions, and improving HCP influenza vaccination rates. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.