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Influenza vaccination among nonhospital healthcare workers (HCWs) is imperative, but only limited data are available for factors affecting their compliance.To examine the factors influencing influenza vaccine compliance among hospital and nonhospital HCWs.A vaccine compliance questionnaire was administered to HCWs working in myriad healthcare settings in March–June 2011.Online and paper surveys were used to assess compliance with the 2010/2011, 2009/2010, and H1N1 influenza vaccines and to examine factors that predicted the uptake of the 2010/2011 seasonal influenza vaccine.In all, 3,188 HCWs completed the survey; half of these (n = 1,719) reported no hospital work time. Compliance rates for all 3 vaccines were significantly higher (P < .001) among hospital versus nonhospital HCWs. In logistic regression stratified by hospital versus nonhospital setting, and when controlling for demographics and past behavior, the determinants of vaccination against the 2010/2011 seasonal influenza among nonhospital-based HCWs included having a mandatory vaccination policy, perceived importance, no fear of vaccine adverse effects, free and on-site access, and perceived susceptibility to influenza. Determinants of hospital-based HCW vaccine compliance included having a mandatory vaccination policy, belief that HCWs should be vaccinated every year, occupational health encouragement, perceived importance of vaccination, on-site access, and no fear of vaccine adverse effects. The strongest predictor of compliance for both worker groups was existence of a mandatory vaccination policy.The reasons for vaccine uptake among nonhospital-based versus hospital-based HCWs differed. Targeted interventions should be aimed at workers in these settings to increase their vaccine compliance, including implementing a mandatory vaccination policy.