We conducted active sentinel surveillance in Monroe County, New York, USA, to compare incidence of community-associated Clostridium difficile infections (CA-CDIs) with that of health care-associated infections (HA-CDIs) and identify exposure and strain type differences between CA and HA cases. Patients positive for C. difficile toxin and with no documented health care exposure in the previous 12 weeks were defined as possible CA case-patients. Patients with onset in a health care setting or recent health care exposure were defined as HA case-patients. Eighteen percent of CDIs were CA; 76% were in persons who reported antimicrobial drug use in the 12 weeks before CDI diagnosis. Strain type distribution was similar between CA and HA cases; North American pulsed-field 1 was the primary strain (31% CA, 42% HA; p = 0.34). CA-CDI is an emergent disease affecting patients recently exposed to antimicrobial drugs. Community strains are similar to those found in health care settings.