Objectives: Toestimate the risks of community-associated Clostridium difficile infection (CA-CDI)amongthe populatioaged =65 years associated with antibiotic exposure and care home residence. Population and methods:We linked cases froma prospective study in Tayside, Scotland from1 November 2008 to 31 October 2009 to population datasets to conduct a cohort study and a nested, matched (1:10 by age and gender) case-control study. Results: There were 79039 eligible residents. CA-CDI incidencewas 20.3/10000 person years. In the cohort study, after adjustment,wefound a significantly increasing risk of CA-CDI with increasing age and comorbidity, prior hospital admission, care home residence [hazard ratio (HR) 1.96, 95% CI 1.14-3.34] and baseline antibiotic exposure (1.94, 1.35-2.77). In separate adjusted models, '4C' antibiotics (clindamycin, co-amoxiclav, cephalosporins, ciprofloxacin; 2.75, 1.78-4.26) and fluoroquinolones (3.33, 1.95-5.67) had higher associated risks. We matched 62 CA-CDI cases without recent (prior 3 months) hospital admission to 620 controls. In adjusted logistic regression models, exposure to any antibiotics increased the risk of CA-CDI (OR 6.04, 95% CI 3.19-11.43). Exposure to 4C antibiotics or fluoroquinolones had higher associated risks: adjusted OR 11.60 (95% CI 5.57-24.15) and 13.04 (4.91-34.64), respectively. Risk of CA-CDI increased with cumulative antibiotic exposure. Subgroup analysis of 42 cases with C. difficile cultured and 420 controls amplified all associations between antibiotic exposure and CA-CDI. Care home residence independently increased the risk of CA-CDI in all models. Conclusions: Our results have two important implications. First, they validate the classification of 4C antibiotics and fluoroquinolones in primary care as high risk for CA-CDI. Second, they demonstrate the importance of prior antibiotic exposure and place of residence for risk assessment by primary care prescribers. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.