OBJECTIVE To improve hand hygiene (HH) compliance among physicians and nurses in a rural hospital in sub-Saharan Africa (SSA) using the World Health Organization's (WHO's) Guidelines on Hand Hygiene in Health Care. DESIGN This study was a quasi-experimental design divided into 4 phases: (1) preparation of materials and acquisition of the hospital administration's support, (2) baseline evaluation, (3) intervention, and (4) follow-up evaluation. SETTING A 160-bed, non-referral hospital in Gitwe, Rwanda PARTICIPANTS A total of 12 physicians and 54 nurses participated in this study. METHODS The intervention consisted of introducing locally produced alcohol-based hand rub (ABHR); educating healthcare workers (HCWs) on proper HH practice; providing pocket-sized ABHR bottles for HCWs; placing HH reminders in the workplace; and surveying HCWs at surrounding health centers regarding HH compliance barriers. Hand hygiene infrastructure, compliance, and knowledge were assessed among physicians and nurses using baseline observations and a follow-up evaluation survey. RESULTS Overall, HH compliance improved from 34.1% at baseline to 68.9% post intervention (P.05). CONCLUSION Hand hygiene campaigns using WHO methods in SSA have been implemented exclusively in large, referral hospitals. This study shows that an HH program using the WHO tools successfully improved HH in a low-income, rural hospital in SSA. Infect Control Hosp Epidemiol 2016;37:834-839.