The outcomes of hospitalization in the Fontan population have not been specifically studied. The purpose of this study was to describe outcomes of hospitalization (frequency and indications for hospitalization, and in-hospital mortality) in this population and to determine how these outcomes differ from those of other adults with congenital heart disease (CHD). Methods: This was a retrospective study of adult Fontan patients hospitalized at Mayo Clinic Rochester in 1990-2015. We selected age- and gender-matched control group of patients with repaired CHD and biventricular circulation hospitalized within the study period. Results: A total of 367 Fontan patients (age 31 ± 7 years and 259 [71%] with atriopulmonary Fontan) had 853 hospital admissions in 4 years (58 hospitalizations per 100 patient-years). The most common indications were arrhythmia (n = 188, 22%), heart failure (n = 169, 20%), and cardiac surgery (n = 133, 16%). Overall in-hospital mortality was 4% (n = 38), and the highest in-hospital mortality occurred in patients hospitalized for cardiac surgery (n = 15, 11%) and heart failure (n = 13, 8%). In comparison to the repaired CHD and biventricular circulation group, the Fontan group had more frequent hospitalizations (22 vs 58 per 100 patient-years, P <.001) and higher overall in-hospital mortality (1% vs 5%, P <.001), mortality after cardiac surgery (2% vs 11%, P =.01), and mortality for heart failure–related hospitalizations (2% vs 8%, P =.04). Conclusions: Adults with Fontan palliation had more frequent hospitalization and in-hospital mortality compared to the rest of the CHD population. Arrhythmia and heart failure were the most common indications for hospitalization. Perhaps optimal management of heart failure and arrhythmia may improve outcomes in this population.