A retrospective study was conducted to assess the relationships between clindamycin resistance in members of the Bacteroides fragilis group, previous antimicrobial therapy, and the context for the development of infection, whether in the community or during hospitalization. Eighty-five clindamycin-resistant clinical strains (one isolate per patient) isolated from January 1988 to October 1994 were matched (one to one) with clindamycin-susceptible isolates recovered during the same period, and the charts of the patients from whom the isolates were recovered were reviewed retrospectively. Of the clindamycin-resistant strains, 65% were recovered from patients with hospital-acquired infections compared with 40% of the clindamycin-susceptible strains (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.41-5.38; P = .002). Prior antimicrobial therapy for > or = 48 hours was also associated with clindamycin resistance (OR, 2.33; 95% CI, 1.16-4.70; P = .02). However, clindamycin resistance remained associated with hospital-acquired infections independent of prior antimicrobial therapy (Mantel-Haenszel weighted average OR, 2.22; 95% CI, 1.03-4.89; P = .04). Clinicians should consider the risks for clindamycin resistance when treating hospital-acquired infections caused by members of the B. fragilis group.