Background: Pressure measurement in total cavopulmonary connection (TCPC) patients is a domain of cardiac catheterization. 4D velocity encoded cardiovascular magnetic resonance (4D-flow MRI) offers an alternative for assessment of even minor pressure differences. The scope of this study was to measure even minor pressure differences in the anastomosis of TCPC patients, who are clinically uncompromised. Methods: Twenty-four patients (median 15 years [8; 34]) with TCPC were studied prospectively by 4D-flow MRI. Pressure differences between superior vena cava (SVC) and extracardiac conduit (C) to both right pulmonary artery (RPA) and left pulmonary artery (LPA) were assessed. Small fluid obstructions as vortices within the anastxomosis were detected by flow pathlines from 4D-flow MRI. In two patients pressure differences were calculated also by computational flow dynamics (CFD) as a plausibility check for the order of magnitude. Results: Median values of pressure differences in the anastomosis between SVC and RPA were 0.63 (0.21-2.1) mmHg, between C and RPA 0.67 (0.3-2.2) mmHg, between SVC and LPA 0.8 (0.3-2.4) mmHg and between C and LPA 0.7 (0.2-1.9) mmHg. Patients with potential flow obstruction (stents, occluder, vortices) had significantly higher gradients at the anastomosis (p < 0.05) than patients without potential obstructions, although the absolute values were small. CFD- and measurement-based pressure difference showed good agreement. Conclusion: 4D-flow MRI is able to detect minor pressure differences within the Fontan circuit even in patients with apparently satisfactory TCPC. Slightly higher pressure differences are due to the presence of small flow obstruction.