Obesity has become increasingly recognized in adults with Fontan palliation, yet the relationship between weight changes in adulthood and Fontan failure is not clearly defined. We hypothesize that increasing weight in adulthood among Fontan patients is associated with the development of Fontan failure. Single-center data from adults with Fontan palliation who were not in Fontan failure at their first clinic visit in adulthood and who received ongoing care were retrospectively collected. Fontan failure was defined as death, transplant, diagnosis of protein losing enteropathy, predicted peak VO₂ less than 50%, or new loop diuretic requirement. Anthropometric data including weight and BMI were collected. Change in weight was compared between those that developed Fontan failure, and those that remained failure-free. To estimate the association between weight change during adulthood and the risk of developing Fontan failure, a survival analysis using multiple Cox’s proportional hazards regression model was performed. Overall, 104 patients were included in the analysis. Those that developed Fontan failure had a larger associated median weight gain than those who remained failure-free (7.8 kg vs. 4.9 kg, respectively; p = 0.011). In multivariable Cox regression analysis, increased weight during adulthood was associated with increased likelihood of developing Fontan failure (HR 1.36; CI 1.07–1.73; p = 0.011). Weight gain in adulthood is associated with the development of Fontan failure.