Objective To compare the therapy effect between surgical therapy and endoscopic therapy for chronic pancreatitis (CP) combined with pancreatic ductal stones (PDS). Methods Clinical data of 113 cases of CP combined with PDS who got treatment in Southwest Hospital of The Third Military Medical University between January 2010 and December 2015 were analyzed retrospectively, 84 of them underwent surgery (surgery group), and 29 of them got endoscopic therapy (endoscopy group). Results The operative time, intraoperative bleeding volume, postoperative hospital stay, and days in hospital, mortality, incidence of complication (pancreatic fistula, delayed gastric emptying, diabetes mellitus, and acute pancreatitis) of the surgery group were all higher than those of endoscopy group (P ＜0.05), but the ratios of the two-stage surgery and recurrence of PDS were all lower (P ＜00.05). The differences between symptom remission rate and residual stones rate were not statistically significant (P>0.05). Conclusions For cases of CP combined with PDS, the clinical therapy effect in symptom remission and residual stones between surgical and endoscopic therapy is similar, but compared with the endoscopic therapy, the operative time, intraoperative bleeding volume, postoperative hospital stay, and days in hospital of the surgical therapy are both longer. However, the ratios of the two-stage surgery and recurrence of PDS in the endoscopy group is significantly higher than those of surgery group.