A study of 240 consecutive admissions to a single hospital ward over a 6-month period was conducted to determine the prevalence of and risk factors for Clostridium difficile colonization at admission. The prevalence rate of C. difficile colonization at admission was 13.3%. Seventy-four percent of the patients admitted to the ward were infected with human immunodeficiency virus (HIV). Multivariate analysis identified three risk factors for C. difficile colonization: clindamycin use (adjusted odds ratio [OR], 9.4; P < .001), penicillin use (adjusted OR, 3.9; P = .018), and a history of cytomegalovirus infection (adjusted OR, 4.2; P = .02). C. difficile colonization at admission to our infectious diseases ward was common. Antibiotic treatments received before admission were the main risk factors for C. difficile colonization. HIV infection per se was not associated with C. difficile colonization. It is interesting that there was an association between C. difficile colonization and a history of cytomegalovirus infection.