Background: The population of adults with congenital heart defects (ACHD) is growing. The leading cause of premature death in these patients is heart failure (HF). However, there is still limited information on the predictive factors for HF in ACHD patients. Objectives: This study re-examined a group of patients with repaired or palliated congenital heart defects (CHD) that were initially studied in 2003. A follow-up period of 15 years has allowed us to identify and evaluate predictors for the development of HF in ACHD. Methods: All patients with repaired or palliated CHD who participated in the initial study (n = 364) were invited for a follow-up examination. The effects of maximum oxygen uptake (VO{}_{\text{2max}}) during exercise stress testing, the cardiac biomarker N-terminal pro brain natriuretic peptide (NT-proBNP), and QRS complex on the development of HF during the follow-up period were investigated. Results: From May 2017 to April 2019, 249 of the initial 364 (68%) patients participated in the follow-up study. Of these, 21% were found to have mild CHD, 60% had moderate CHD, and 19% had complex CHD. Significant predictors for the development of HF were: NT-proBNP level >1.7 times the upper normal limit, VO{}_{\text{2max}} 73% of predicted values, and QRS complex duration >120 ms. Combination of these three parameters resulted in the highest area-under-the-curve of 0.75, with a sensitivity of 75% and specificity of 63% for predicting the development of HF. Conclusions: In this cohort of ACHD patients, the combination of VO{}_{\text{2max\%}}, NT-proBNP, and QRS duration was predictive of HF development over a 15-year follow-up period. Enhanced surveillance of these parameters in patients with ACHD may be beneficial for the prevention of HF and early intervention.