Although educational programs could enhance knowledge, practices, and compliance with hand hygiene (HH) for health care workers, the researches focusing on effective methods for educating and increasing the compliance with HH practices are scanty. Consequently, the researchers conducted the present study to assess HH-related knowledge, attitude, and compliance rate after the implementation of a modified version of the World Health Organization (WHO) multimodal strategy was written in the background. A pretest-posttest quasiexperimental study was conducted in a university hospital in Cairo among 84 nurses. The study consisted of 4 phases: baseline assessment, intervention, postintervention assessment, and follow-up phase. The intervention (HH-campaign) consisted of 4 components: infrastructure change, training/education of health care workers, posting visual reminders, and development of institutional safety climate "hand hygiene champions." HH compliance rate significantly increased from 28% before the intervention to 50% after the intervention and 58% after the follow-up period (P < .001). The knowledge score and the attitude score significantly improved before and after the intervention (P < .001). The use of alcohol handrub significantly increased from 9.5% before the intervention to 65% after the intervention and 76% after the follow-up period. Implementation of a modified version of the World Health Organization multimodal strategy successfully doubled HH compliance rates. Tackling a social way of thinking together with regular frequent training and follow-up are essential to sustain adherence to safe HH practices.