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Background: There is limited knowledge about risk factors for Clostridioides difficile infection (CDI) and recurrent CDI in solid organ transplant (SOT) recipients., Methods: A case-control study of CDI in SOT recipients compared with controls (SOT recipients who did not present CDI)., Results: Sixty-seven patients from 1089 SOT recipients (6.2%) suffered at least one episode of CDI. The mean age was 55 ± 12 years and 20 cases (69%) were men. The accumulated incidence was 8% in liver transplantation, 6.2% in lung transplantation, 5.4% in heart transplantation, and 4.7% in kidney transplantation. Twenty-nine cases (43.3%) were diagnosed during the first 3 months after SOT. Forty-one cases (61.2%) were hospital acquired. Thirty-one patients with CDI presented with mild-moderate infection (46.3%), 30 patients with severe infection (44.8%), and 6 patients with severe-complicated disease (9%). Independent variables found to be related with CDI were hospitalization in the previous 3 months (odds ratio: 2.99; [95% confidence interval 1.21-7.37]) and the use of quinolones in the previous month (odds ratio: 3.71 [95% confidence interval 1.16-11.8]). Eleven patients (16.4%) had at least one recurrence of CDI. Previous treatment with amoxicillin-clavulanate, severe-complicated index episode, and high serum creatinine were associated with recurrent CDI in the univariant analysis CONCLUSIONS: Liver transplant recipients presented the highest incidence of CDI among SOT recipients. Risk factors for CDI were hospitalization in the previous 3 months and the use of quinolones in the previous month., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)