Objective To investigate the association between preoperative, operative, and postoperative factors and persistent pleural effusion after the extracardiac Fontan procedure. Methods Ninety-five consecutive patients diagnosed with univentricular heart underwent extracardiac connection using Gore-Tax conduits at the Department of Children's Heart Centre, Justus-Liebig-University Giessen in Germany from June 1996 to July 2007. The outcome measures were duration and volume of chest tube drainage after surgical intervention. The investigated factors included age and weight at the time of operation, anatomical diagnosis, preoperative oxygen saturation, mean pulmonary artery pressure, ventricular end-diastolic pressure, fenestration, cardiopulmonary bypass time, conduit size, postoperative pulmonary artery pressure, administration of angiotensin-converting enzyme inhibitors, and postoperative infection. Associations between these factors and persistent pleural effusion after the extracardiac Fontan procedure were analyzed. Results Every patient suffered postoperative effusion. The median duration of postoperative chest tube drainage was 9 days (range, 3-69 days), and the median volume was 12 mL·kg −1·d −1 (range, 2.0-37.5 −1·d −1). Thirty-seven (38.9%) patients had pleural drainage for more than 15 days, and the volume in 35 (36.8%) patients exceeded 25 mL·kg −1·d −1. Nineteen (20%) patients required placement of additional chest tubes for re-accumulation of pleural effusion after removal of previous chest tubes. Fifteen (17.8%) patients were hospitalized again due to pleural effusion after discharge. The median length of hospital stay after the operation was 14 days (range, 4-78 days). Multivariate analysis results showed that non-fenestration, low preoperative oxygen saturation, and postoperative infections were independent risk factors for prolonged duration of pleural drainage ( P<0.05). Long cardiopulmonary bypass time, non-fenestration, small conduit size, and low preoperative oxygen saturation were independent risk factors for excessive volume of pleural drainage ( P<0.05). Conclusions For reduing postoperative duration and volume of pleural drainage following Fontan procedure, it seems to be important to improve the preoperative oxygen saturation, use large size of conduit, shorten cardiopulmonary bypass time, and make fenestration during the operation, as well as avoid postoperative infections.