Objective: To investigate the value and operative approach of liver resection for intrahepatic bile duct stones. Methods: The operative approaches and outcomes in 442 patients with hepatolithiasis, 410 of whom had concomitant extrahepatic cholangiolithiasis, admitted during the past 3 years, were retrospectively analyzed. Results: Of the 442 patients, 206 cases underwent hepatic lobectomy (group A), and the other 236 cases received choledocholithotomy only (group B). One patient in each group died after operation. The incidence of complications related to surgery was 8.8% (18/205) in group A and 11.1% (26/235) in group B respectively, and the difference between them had no statistical significance (χ2=0.634, P=0.263). The rate of retained stones was 16.1% (33/205) in group A and 46.8% (96/235) in group B respectively, and the difference between the two groups had statistical significance (χ2=32.4, P<0.001). In group A, the rate of residual stones was associated with the distribution of stones in the intrahepatic bile ducts (χ2=14.0, P=0.001), but irrelevant to whether anatomical lobectomy was performed or not (χ2=0.892, P=0.451). Seven cases in group A were found to have intrahepatic cholangiocarcinoma, and successfully underwent surgical resection of the tumors. In group B, 4 cases were found to have liver tumors after a follow-up of 2 years, and 2 of them underwent surgical resection. The total number of cases of recurrent cholangiolithiasis, biliary obstruction or infection after follow-up of more than 2 years was 16 (8.1%) in group A and 62 (26.8%) group B respectively, and the difference had statistical significance (χ2=25.2, P<0.001); of the 16 cases in group A, only one case was from those undergoing anatomical lobectomy and the other 15 cases were from those receiving partial hepatectomy, which showed significant difference (P=0.043). Conclusion: Hepatic lobectomy can reduce the rate of postoperative residual stones in patients with hepatolithiasis. Further, the anatomical hepatolobectomy can apportunely resect latent malignant lesions, and also effectively decrease the long-term chance of recurrence of biliary stones, obstruction and infection.