Background: Although hand hygiene (HH) has proven to be an effective measure to prevent infections, HH compliance is generally low. We assessed sociocognitive determinants of caregivers' HH behavior in child day care centers (DCCs) to develop an effective HH intervention. Methods: Caregivers' compliance to HH guidelines was observed. Observed caregivers completed a questionnaire on self-reported HH compliance, sociocognitive determinants, and sociodemographic data. To determine sociocognitive determinants of observed compliance, multilevel logistic regression analyses were performed. Self-reported compliance was analyzed using linear regression. Results: In 122 participating DCCs, 350 caregivers and 2,003 HH opportunities were observed. The response rate on the questionnaire was 100%. Overall observed HH compliance was 42% (841/2,003). Overall mean self-reported HH compliance was 8.7 (scale, 0-10). Guideline knowledge (odds ratio [OR], 1.27; 95% confidence interval [CI]: 1.03-1.56) and perceived disease severity (OR, 0.93; 95% CI: 0.87-0.99) were associated with observed compliance. Guideline knowledge (β = 0.31; P <.001), guideline awareness (β = 0.16; P <.001), perceived importance (β = 0.20; P =.004), perceived behavioral control (β = 0.24; P <.001), habit (β = 0.27; P <.001), and children at home (β = 0.30; P =.002) were associated with self-reported compliance. Conclusion: When developing HH interventions for caregivers in DCCs, improving guideline knowledge should be considered as this was associated with both observed and self-reported HH compliance. Furthermore, increasing guideline awareness, perceived importance, and perceived behavioral control can contribute to better HH, as well as making HH a habitual behavior. Copyright © 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc.