AbstractObjective:To assess the effect of a multimodal intervention on hand hygiene compliance (HHC) in nursing homes.Design, setting, and participants:HHC was evaluated using direct, unobtrusive observation in a cluster randomized controlled trial at publicly funded nursing homes in the Netherlands. In total, 103 nursing home organizations were invited to participate; 18 organizations comprising 33 nursing homes (n = 66 nursing home units) participated in the study. Nursing homes were randomized into a control group (no intervention, n = 30) or an intervention group (multimodal intervention, n = 36). The primary outcome measure was HHC of nurses. HHC was appraised at baseline and at 4, 7, and 12 months after baseline. Observers and nurses were blinded.Intervention:Audits regarding hand hygiene (HH) materials and personal hygiene rules, 3 live lessons, an e-learning program, posters, and a photo contest. We used a new method to teach the nurses the WHO-defined 5 moments of HH: Room In, Room Out, Before Clean, and After Dirty.Results:HHC increased in both arms. The increase after 12 months was larger for units in the intervention arm (from 12% to 36%) than for control units (from 13% to 21%) (odds ratio [OR], 2.10; confidence interval [CI], 1.35–3.28). The intervention arm exhibited a statistically significant increase in HHC at 4 of the 5 WHO-defined HH moments. At follow-up, HHC in the intervention arm remained statistically significantly higher (OR, 1.93; 95% CI, 1.59–2.34) for indications after an activity (from 37% to 39%) than for indications before an activity (from 14% to 27%).Conclusions:The HANDSOME intervention is successful in improving HHC in nursing homes.