Background: Endocystectomy is a conservative surgical approach to managing cystic echinococcosis. Bile leakage is the main complication of this technique. The aim of this study was to evaluate the factors associated with bile leakage and to assess the outcomes and cost efficiency of strategies used to treat bile leakage. Methodology/Principal findings: Patients who underwent endocystectomy between 2005 and 2020 were included. The preoperative characteristics, intra- and postoperative outcomes, hospital costs, and cost efficiency (the Diagnosis-Related Group reimbursement minus the overall cost) were evaluated prospectively. A total of eighty patients with 142 cysts were included. Postoperative complications occurred in 17 patients (21%), including 11 patients with bile leakage (type A: 1, type B: 6 and type C: 4 patients, total 13%). Bile leakage was more frequent in patients with preoperative MRI signs of cysto-biliary fistulas or intraoperative visible cysto-biliary fistulas (p = 0.03 and p = 0.04, respectively) and in patients with cysts larger than 8 cm (p = 0.03). Patients with bile leakage who underwent reoperation (type C) had significantly shorter hospital stays (9 vs. 16 days, p<0.01) and better cost efficiency than those who received radiologic or endocscopic interventions (€2,072 vs. -€2,097 p = 0.01). No mortality was observed, and recurrence was seen in two patients. Conclusions/Significance: Endocystectomy is a safe and efficient technique. Preoperative and intraoperative cysto-biliary fistulas and a cyst diameter larger than 8 cm are correlated to postoperative bile leakage. Early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments. Author summary: Endocystectomy is a conservative surgical approach to managing hepatic cystic echinococcosis (CE). Bile leakage is the major complication of this technique. In the current study, we evaluated the patients who underwent endocystectomy and assessed the factors associated with bile leakage. The operative and postoperative outcomes and cost efficiency of strategies, which was used to treat bile leakage were also evaluated. Eighty patients with 142 cysts were included. Among them eleven patients shown bile leakage. Four patients underwent reoperation to treat bile leakage, while six patients received radiologic intervention. We found that cysto-biliary fistula and cyst size >8 cm correlate with bile leakage after endocystectomy. We also concluded that early operative management of bile leakage reduces hospital stay and improves cost efficiency compared with radiologic or endoscopic treatments. [ABSTRACT FROM AUTHOR]