Objective: To investigate the effects of friendly competition on hand hygiene compliance as part of a multimodal intervention program., Design: Prospective observational study in which the primary outcome was hand hygiene compliance. Differences were analyzed using the Pearson χ2 test. Odds ratios (ORs) with 95% confidence interval were calculated using multilevel logistic regression., Setting: Observations were performed in 9 public hospitals and 1 rehabilitation center in Rotterdam, Netherlands.ParticipantsFrom 2014 to 2016, at 5 time points (at 6-month intervals) in 120 hospital wards, 20,286 hand hygiene opportunities were observed among physicians, nurses, and other healthcare workers (HCWs).InterventionThe multimodal, friendly competition intervention consisted of mandatory interventions: monitoring and feedback of hand hygiene compliance and optional interventions (ie, e-learning, kick-off workshop, observer training, and team training). Hand hygiene opportunities, as formulated by the World Health Organization (WHO), were unobtrusively observed at 5 time points by trained observers. Compliance data were presented to the healthcare organizations as a ranking., Results: The overall mean hand hygiene compliance at time point 1 was 42.9% (95% confidence interval [CI], 41.4-44.4), which increased to 51.4% (95% CI, 49.8-53.0) at time point 5 (P<.001). Nurses showed a significant improvement between time points 1 and 5 (P<.001), whereas the compliance of physicians and other HCWs remained unchanged. In the multilevel logistic regressions, time points, type of ward, and type of HCW showed a significant association with compliance., Conclusion: Between the start and the end of the multimodal intervention program in a friendly competition setting, overall hand hygiene compliance increased significantly.