Acetaminophen poisoning increases cytochrome P450 2E1 expression and reactive oxygen species production, which may lead to maladaptive myocardial remodeling and congestive heart failure (CHF). We conducted a nationwide cohort study to investigate the incidence and risk of CHF in patients with acetaminophen poisoning. We identified a cohort of adult patients with newly diagnosed acetaminophen poisoning in the inpatient claims of the Taiwan National Health Insurance Research Database for the 1998-2011 period. A comparison cohort was frequency matched at a 4:1 ratio for sex, age and index year. All patients were followed up until the occurrence of CHF, withdrawal from the National Health Insurance program, or December 31, 2011. Cox proportional hazards models were employed to calculate the risk of CHF in the acetaminophen poisoning cohort compared with the comparison cohort, and the hazard ratios with 95% confidence intervals are presented. A total of 3546 and 14 184 patients with and without acetaminophen poisoning were followed up for a total of 25 856 and 102 119 person-years, respectively. The overall incidence of CHF was higher in the acetaminophen poisoning cohort than in the comparison cohort (8.12 vs. 5.19 per 10 000 person-years). After adjustment for covariates, the acetaminophen poisoning cohort exhibited a 1.59-fold higher risk of CHF (adjusted hazard ratio = 1.59; 95% confidence interval = 1.43-1.75) than did the comparison cohort. Patients with acetaminophen poisoning exhibited a significantly higher risk of CHF compared with the comparison cohort. Clinicians should follow up heart function in patients with acetaminophen poisoning.