Background: Yinhua Miyanling tablet (YMT) not only has the functions of clearing away heat and toxin, dredging drenching and diuresis, but also has antibacterial activity. The formation of bacterial biofilm in ureteral stent and its related infection have plagued the clinic. Antibacterial traditional Chinese medicine is a potential method. Methods: This multicenter, randomized, double-blind, placebo-controlled study was designed to enroll patients who underwent ureteroscopic lithotripsy associated with indwelling ureteral stents at six centers between March 2019 and June 2020. The eligible patients were randomly assigned to the experimental group to take YMT 2 g qid orally or the control group to take dummy YMT 2 g qid orally from the first day after the operation according to a random number table. The unused drugs were recalled 14 +/- 3 days after the operation and record the body temperature. Relevant laboratory tests (urinalysis and urine culture) were performed before extubation. The ureteral stent was removed. The specimen was collected for scanning electron microscopy (SEM). Biofilm formation, USSQ scores, postoperative infectious complications, stone formation, and adverse drug reactions were compared between the two groups. Results: Of the 211 patients enrolled, 165 were included in the per-protocol set (PPS), including 86 in the control group and 79 in the experimental group. No significant difference was found between the two groups in baseline parameters (P>0.05). The prevalence of biofilm formation in the control group (47%) was significantly higher than that in the experimental group (22.7%, P=0.001). There was no significant difference in total USSQ score and domain score between the two groups (all P>0.05). There were more patients with symptomatic urinary tract infection (UTI) in the control group (12.9%) than in the experimental group (2.6%, P=0.017). The incidence of other complications did not show a significant difference between the two groups (all P>0.05). The incidence of stone formation on the ureteral stent surface and adverse drug reactions did not show a significant difference between the two groups (all P>0.05). Conclusions: YMT is helpful to reduce the formation of bacterial biofilms on ureteral stents and the incidence of symptomatic UTIs related to ureteral stunting after surgery for ureteral calculi.