Hospitalized patients with community-acquired pneumonia (CAP) are at risk of developing Clostridioides difficile infection (CDI). We developed and tested clinical decision rules for identifying CDI risk in this patient population. The study was a single-center retrospective, case-control analysis of hospitalized adult patients empirically treated for CAP between 1 January 2014 and 3 March 2018. Differences between cases (CDI diagnosed within 180 days following admission) and controls (no test result indicating CDI during the study period) with respect to prehospitalization variables were modeled to generate propensity scores. Postadmission variables were used to predict case status on each postadmission day where (i) ≥1 additional case was identified and (ii) each model stratum contained ≥15 subjects. Models were developed and tested using optimal discriminant analysis and classification tree analysis. Forty-four cases and 181 controls were included. The median time to diagnosis was 50 days postadmission. After weighting, three models were identified (20, 117, and 165 days postadmission). The day 20 model yielded the greatest (weighted [w]) accuracy (weighted area under the receiver operating characteristic curve [wROC area] = 0.826) and the highest chance-corrected accuracy (weighted effect strength for sensitivity [wESS] = 65.3). Having a positive culture (odds, 1:4; P = 0.001), receipt of ceftriaxone plus azithromycin for a defined infection (odds, 3:5; P = 0.006), and continuation of empirical broad-spectrum antibiotics with activity against P. aeruginosa when no pathogen was identified (odds, 1:8; P = 0.013) were associated with CDI on day 20. Three models were identified that accurately predicted CDI in hospitalized patients treated for CAP. Antibiotic use increased the risk of CDI in all models, underscoring the importance of antibiotic stewardship.