Objective. To assess the feasibility and effectiveness of the World Health Organization hand hygiene improvement strategy in a low-income African country. Design. A before-and-after study from December 2006 through June 2008, with a 6-month baseline evaluation period and a follow-up period of 8 months from the beginning of the intervention. Setting. University Hospital, Bamako, Mali. Participants. Two hundred twenty-four healthcare workers. Methods. The intervention consisted of introducing a locally produced, alcohol-based handrub; monitoring hand hygiene compliance; providing performance feedback; educating staff; posting reminders in the workplace; and promoting an institutional safety climate according to the World Health Organization multimodal hand hygiene improvement strategy. Hand hygiene infrastructure, compliance, healthcare workers' knowledge and perceptions, and handrub consumption were evaluated at baseline and at follow-up. Results. Severe deficiencies in the infrastructure for hand hygiene were identified before the intervention. Local handrub production and quality control proved to be feasible, affordable, and satisfactory. At follow-up, handrubbing was the quasi-exclusive hand hygiene technique (93.3%). Compliance increased from 8.0% at baseline to 21.8% at follow-up ([Formula: see text]). Improvement was observed across all professional categories and medical specialities and was independently associated with the intervention (odds ratio, 2.50; 95% confidence interval, 1.8-3.5). Knowledge enhanced significantly ([Formula: see text]), and perception surveys showed a high appreciation of each strategy component by staff. Conclusions. Multimodal hand hygiene promotion is feasible and effective in a low-income country. Access to handrub was critical for its success. These findings motivated the government of Mali to expand the intervention nationwide. This experience represents a significant advancement for patient safety in developing countries.