We performed a school-based cluster-randomized, controlled trial at a single elementary school. Eligible students in third to fifth grade were enrolled. Intervention classrooms received alcohol-based hand sanitizer to use at school and quaternary ammonium wipes to disinfect classroom surfaces daily for 8 weeks; control classrooms followed usual hand-washing and cleaning practices. Parents completed a preintervention demographic survey. A total of 285 students were randomly assigned; baseline demographics were similar in the 2 groups. The adjusted absenteeism rate for gastrointestinal illness was significantly lower in the intervention-group subjects compared with control subjects. The adjusted absenteeism rate for respiratory illness was not significantly different between groups. Norovirus was the only virus detected and was found less frequently on surfaces in intervention classrooms compared with control classrooms (9% vs 29%). Pediatrics. 2008;121:1555-62.