OBJECTIVE: To evaluate the effects of the introduction of an alcohol-based hand gel and multifaceted quality improvement (QI) interventions on hand hygiene (HH) compliance. DESIGN: Interventional, randomized cohort study with four study phases (baseline; limited intervention in two units; full intervention in three units; washout phase), performed in three intensive care units at a pediatric referral hospital. METHODS: During 724 thirty-minute daytime monitoring sessions, a nonidentified observer witnessed 12,216 opportunities for HH and recorded compliance. INTERVENTIONS: Introduction of an alcohol-based hand gel; multifaceted QI interventions (educational program, opinion leaders, performance feedback). RESULTS: Baseline compliance decreased after the first 2 weeks of observation from 42.5% to 28.2% (presumably because of waning of a Hawthorne effect), further decreased to 23.3% in the limited intervention phase and increased to 35.1% after the introduction of a hand gel with QI support in all three units (P < 0.001). The rise in compliance persisted in the last phase (compliance, 37.2%); however, a gradual decline was observed during the final weeks. Except for the limited intervention phase, compliance achieved through standard handwashing and glove use remained stable around 20 and 10%, respectively, whereas compliance achieved through gel use increased to 8% (P < 0.001). After adjusting for confounding, implementation of the hand gel with QI support remained significantly associated with compliance (odds ratio, 1.6; 95% confidence interval, 1.4 to 1.8). In a final survey completed by 62 staff members, satisfaction with the hand gel was modest (45%). CONCLUSIONS: We noted a statistically significant, modest improvement in compliance after introduction of an alcohol-based hand gel with multifaceted QI support. When appropriately implemented, alcohol-based HH may be effective in improving compliance.