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Sepsis risk was associated with indwelling medical device use in a rural hospital.Risk factors for sepsis morbidity also included coronary heart disease.Government-issued health insurance had a borderline significance with sepsis risk.Sepsis was most frequently secondary to urinary tract infections and pneumonia.The aim of the study was to identify risk factors for sepsis morbidity in a rural hospital population.We used a case-control study design. Patients included adult admissions to a rural health system between January 1, 2012, and December 31, 2015. Case selection was by electronic medical record search for codes of the ICD-9-CM. Cases were validated against Quick Sequential Organ Failure Assessment criteria. Multiple logistic regression modeling was performed to determine which predefined variables were significantly associated with sepsis diagnosis.A total of 220 patients were studied (110 cases and 110 controls). Cases had an in-hospital mortality of 20% compared with 0% of the controls. Indwelling medical device use during hospitalization (adjusted odds ratio [OR], 3.02; 95% confidence interval [CI], 1.44-6.30; P = .003), coronary heart disease (adjusted OR, 2.59; 95% CI, 1.13-5.97; P = .03), and type of health insurance (adjusted OR, 2.36; 95% CI, 1.13-4.93; P = .02) were independently associated with sepsis diagnosis after adjusting for potential confounders.This study underscores the need for implementation and maintenance of infection control measures during management of patients with indwelling medical devices at a rural hospital.