Background The aim of this study was to compare the outcomes of one-step multichannel percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) with traditional PTCSL in the treatment of bilateral hepatolithiasis. Methods From February 2011 to June 2015, 156 patients with bilateral hepatolithiasis received surgical treatment in our department. Among these patients, 81 received one-step multichannel PTCSL (group A), and the remaining 75 received traditional PTCSL (group B). Results Compared with group B, group A was characterized by a significantly shorter operation time (83.7 +/- 28.5 min vs 118.1 +/- 41.5 min; P = 0.000), hospital stay (11.1 +/- 3.4 d vs 17.8 +/- 5.6 d; P = 0.034), and postoperative hospital stay (6.9 +/- 3.1 d vs 9.6 +/- 4.5 d; P = 0.026). In addition, the immediate clearance (62.9% vs 45.3%, P = 0.027) and final clearance (90.1% vs 78.7%, P = 0.048) rates were higher in group A than in group B. During the follow-up period, stone recurrence was significantly less common in group A than in group B (13.6% vs 26.7%, P = 0.041). Multivariate Cox analysis showed that the PTCSL method (HR = 2.32, 95% confidence interval [CI] = 1.09-4.90, P = 0.028), bilateral biliary stricture (HR = 4.17, 95% CI = 1.73-10.03, P = 0.001), and stones located in segments I (HR = 7.75, 95% CI = 3.67-16.38, P = 0.000) were independent predictors of recurrence. Conclusions Compared with traditional PTCSL, one-step multichannel PTCSL was more efficient and effective in the treatment of bilateral hepatolithiasis.