Recurrence is a common sequela ofClostridium difficile-associated diarrhea (CDD) and may increase morbidity, costs, and treatment-related antimicrobial resistance. Because recurrent CDD (RCDD) frequently occurs very soon after an initial episode, our goal was to determine the risk factors forearlyRCDD (occurring ≤45 days after the initial episode). We conducted a case-control study, comparing 13 patients with early RCDD (case patients) with 46 patients who had only one CDD episode (control patients) at Centre Hospitalier Angrignon (Québec) during January 1993 through November 1994. Risk factors for early RCDD included a history of chronic renal insufficiency, a white blood cell count of ≥ 15 × 103/mm3, and community-acquired diarrhea with the first CDD episode. For seven of eight case patients,C. difficilestrains from the first and second CDD episodes were identical, suggesting that relapse is more common than reinfection. These results suggest that treatments should be directed at preventing relapses in patients at high risk for early RCDD.