Hand hygiene is the most cost-effective and simple measure of preventing healthcare associated infections (HAI). The approach to improve low compliance must be through multimodal interventions such as the "Clean Care is Safer Care" strategy (WHO).To estimate the efficacy of a multimodal strategy in improving hand hygiene in five wards of a tertiary care hospital in Medellín, Colombia (2008-2010).Quasi-experimental before-after study.Hand hygiene compliance significantly increased after the intervention (82 to 89%, p = 0.007). The knowledge score increased from a median of 26 (IQR=22-28) to 30 (IQR=26-32, p = 0.001). Alcohol-based hand rub consumption increased significantly from 10.5 liters to 58.1 liters per 1000 patient-days [incidence ratio (IR) = 2.39, 95% CI = 1.99; 2.88]. Monthly HAI rates showed no significant variations during the same period [IR = 0.90, 95% CI = 0.71; 1.13].This and other recent studies demonstrate that implementing a multimodal strategy for hand hygiene significantly increases compliance with this measure, irrespective of type of health worker or hospital department.Implementing a multimodal strategy we achieved significant increases in hand hygiene compliance but mild or no significant variations in monthly HAI rates.