Necrotizing pancreatitis (NP) patients commonly require antibiotic treatment during the several month-long disease course. We hypothesized that Clostridium difficile infection (CDI) is common in NP and significantly impacts outcomes. Retrospective review of 704 NP patients treated at a single-institution (2005-2018). 10% (67/704) of patients developed CDI a mean 78 days after NP onset. Patients developing CDI experienced increased total hospital days (CDI, 104; No CDI, 42; P < 0.001), readmission rates (CDI, 85%; No CDI, 64%; P = 0.006), and duration of NP (CDI, 248 days; No CDI, 183; P = 0.001). Risk factors for CDI included antibiotic use (OR, 96.2; 95% CI, 5.9-1556.2; P = 0.001) and any organ failure (OR, 2.0; 95% CI, 1.2-3.3, P = 0.008). Mortality was not affected by CDI (CDI, 10%; No CDI, 9%; P = 0.7). Clostridium difficile infection is common in necrotizing pancreatitis and negatively impacts morbidity and disease recovery. Copyright © 2019 Elsevier Inc. All rights reserved.