Objective To observe the effects of modified Jianpi Yishen Decoction on urinary osteopontin (OPN) in calcium oxalate nephrolithiasis patients after percutaneous nephrolithotomy (PCNL) or ureteroscope lithotomy (URL);To clarify the mechanism of modified Jianpi Yishen Decoction on the prevention of calcium oxalate kidney stones. Methods Totally 116 calcium oxalate nephrolithiasis patients were randomly divided into trial group (62 cases) and control group (54 cases). The trial group took modified Jianpi Yishen Decoction every other day, while the control group took potassium sodium hydrogen citrate granules three times a day. The concentrations of OPN, urinary calcium and urinary oxalic acid of the patients in the two groups were observed before treatment and 2 weeks and 4 weeks of treatment. Results The concentration of urinary OPN of 2 weeks and 4 weeks of the treatment in the trial group was significantly increased compared with before treatment (P<0.05), and the difference was statistically significant compared with the control group (P<0.05). The concentration of urinary OPN in the control group had no significant change after treatment (P>0.05). The differences in the concentrations of urinary calcium and urinary oxalic acid of the two groups between before and after treatment were not significant (P>0.05). Conclusion Modified Jianpi Yishen Decoction can effectively restrain the formation of the calcium oxalate stones by increasing the level of urinary OPN, which demonstrates effective prevention in the calcium oxalate nephrolithiasis patients after PCNL or URL.