Postoperative prolonged pleural effusion (PPE) remains a confounding problem after a Fontan operation. We aimed to describe the risk factors for PPE after a Fontan operation and to clarify the impact of prophylactic opening of the pleural cavity (POPC) for drainage tube insertion on PPE. We retrospectively reviewed the medical charts of 50 consecutive patients who underwent a Fontan operation at our institution. POPC for postoperative drainage was performed based on each surgeon’s preference. Patients were divided into three groups for analysis: group A (n = 12), no opening; group B (n = 14), unilateral opening; and group C (n = 24), bilateral opening. At the time of surgery, the median age of our patient group was 26 months, with a median body weight of 10.5 kg. The volume of pleural effusion tended to be lower in group A than in groups B and C (p = 0.08). The median duration of drainage was significantly shorter (p = 0.03) in group A (3 days) than in group B (4 days) or C (5 days). Overall, 12 patients required chest tube drainage for ≥ 7 days. Multivariate analysis revealed POPC (p = 0.01) and postoperative water balance (p = 0.03) as independent predictors of PPE. POPC and postoperative water balance are risk factors for PPE after a Fontan operation. Therefore, avoiding POPC for postoperative drainage may reduce the risk of postoperative pleural effusion and morbidities associated with PPE after a Fontan operation.