Background: We assessed the effectiveness of a handwashing program using hand sanitizer to prevent school absenteeism due to upper respiratory infections (URIs). Methods: This was a randomized, controlled, and open study on a sample of 1341 children 4-12 years old, attending 5 state schools in Almería (Spain), with an 8-month follow-up. The experimental group (EG) washed their hands with soap and water, together with using hand sanitizer, and the control group followed their usual handwashing procedures. Absenteeism rates due to URIs were compared between the 2 groups through a multivariate Poisson regression analysis. The percent of days missed in both groups were compared with a z test. Results: Overall, 1271 cases of school absenteeism due to URIs were registered. Schoolchildren from the EG had a 38% lower risk of absenteeism due to URIs, incidence rate ratio: 0.62, 95% confidence interval: 0.55-0.70, and a decrease in absenteeism of 0.45 episodes/child/academic year, p < 0.001. Pupils missed 2734 school days due to URIs and the percentage of days absent was significantly lower in the EG, p < 0.001. Conclusions: Use of hand sanitizer plus handwashing with soap accompanied by educational support is an effective measure to reduce absenteeism due to URIs