BACKGROUND: Acute bacterial cellulitis is a potentially serious infection that commonly recurs. The identification of preventable risk factors could reduce infection-related morbidity and cost and improve patient management. The aim of this study was to identify the risk factors associated with lower-limb cellulitis, including both analysis of risk factors associated with cellulitis in either limb and risk factors in a single limb associated with cellulitis in the same limb. We placed particular emphasis on dermatophytic infections of the foot and bacterial infection and colonization of the toe webs. METHODS: We conducted a prospective case-control study of 100 subjects with cellulitis and 200 control subjects, matched for age and sex, who were admitted to a university hospital during the period October 2000-February 2004. Data were obtained with a questionnaire and from examination of lower limbs and microbiological analyses of samples from the feet. RESULTS: The median age of the participants was 66.5 years (interquartile range, 48.8-77.0). The following risk factors were strongly and independently associated with cellulitis: previous history of cellulitis (OR, 31.04; 95% CI, 4.15-232.20), the presence of Staphylococcus aureus and/or beta -hemolytic streptococci in the toe webs (OR, 28.97; 95% CI, 5.47-153.48), presence of leg erosions or ulcers (OR, 11.80; 95% CI, 2.47-56.33), and prior saphenectomy (OR, 8.49; 95% CI, 1.62-44.52). Tinea pedis interdigitalis was associated with cellulitis only when toe web bacteria were excluded from the analysis (OR, 3.86; 95% CI, 1.32-11.27). CONCLUSIONS: Risk factors for acute bacterial cellulitis in hospitalized patients include predisposing factors and the presence of sites of pathogen entry on legs and toe webs. These findings indicate that improved awareness and management of toe web intertrigo, which may harbor bacterial pathogens, and other skin lesions might reduce the incidence of cellulitis.