Background Atrial fibrillation (AF) of new onset during acute illness (AFNOAI) has a variable incidence of 1%–44% in hospitalized patients. This study assesses the risk factors for persistence of AFNOAI in the 5 years after hospital discharge for critically ill patients. Methods This was a retrospective cohort study. All patients ≥18 years old admitted to the medical intensive care unit (MICU) of a tertiary care hospital from January 1, 2012, to October 31, 2015, were screened. Those designated with AF for the first time during the hospital admission were included. Risk factors for persistent AFNOAI were assessed using a Cox’s proportional hazards model. Results Two-hundred and fifty-one (1.8%) of 13,983 unique MICU admissions had AFNOAI. After exclusions, 108 patients remained. Forty-one patients (38%) had persistence of AFNOAI. Age (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01–1.08), hyperlipidemia (HR, 2.27; 95% CI, 1.02–5.05) and immunosuppression (HR, 2.29; 95% CI, 1.02–5.16) were associated with AFNOAI persistence. Diastolic dysfunction (HR, 1.46; 95% CI, 0.71–3.00) and mitral regurgitation (HR, 2.00; 95% CI, 0.91–4.37) also showed a trend towards association with AFNOAI persistence. Conclusions Our study showed that AFNOAI has a high rate of persistence after discharge and that certain comorbid and cardiac factors may increase the risk of persistence. Anticoagulation should be considered, based on a patient’s individual AFNOAI persistence risk.