ABSTRACT Objective: To evaluate the effects that a hand hygiene education program has on the compliance of health professionals in an ICU. Methods: This was a quasi-experimental study with an interrupted time-series design, conducted over a 12-month period: the 5 months preceding the implementation of a hand hygiene education program (baseline period); the 2 months of the intensive (intervention) phase of the program; and the first 5 months thereafter (post-intervention phase). Hand hygiene compliance was monitored by one of the researchers, unbeknownst to the ICU team. The primary outcome measure was the variation in the rate of hand hygiene compliance. We also evaluated the duration of mechanical ventilation (MV), as well as the incidence of ventilator-associated pneumonia (VAP) at 28 days and 60 days, together with mortality at 28 days and 60 days. Results: On the basis of 959 observations, we found a significant increase in hand hygiene compliance rates-from 31.5% at baseline to 65.8% during the intervention phase and 83.8% during the post-intervention phase, corresponding to prevalence ratios of 2.09 and 2.66, respectively, in comparison with the baseline rate (p < 0.001). Despite that improvement, there were no significant changes in duration of MV, VAP incidence (at 28 or 60 days), or mortality (at 28 or 60 days). Conclusions: Our findings indicate that a hand hygiene education program can increase hand hygiene compliance among ICU professionals, although it appears to have no impact on VAP incidence, duration of MV, or mortality.