Introduction: Using a safety wire during trans-ureteral lithotripsy (TUL) might minimize ureteral injuries. Conversely, others suggest safety wire itself may increase the risk of ureteral injuries that its routine use is not mandatory in all cases. This randomized clinical trial was conducted to compare the outcome of TUL in the presence or absence of a safety guidewire. Methods: This randomized clinical trial was conducted on patients referred to our center with a ureteral stone less than 1.5 cm; candidate for TUL after not passing the stone after 2 weeks of conservative management and had no sign of infections or anatomic abnormalities. The primary outcome was the rate of ureteral injuries. Patients were randomly divided into two groups; using safety wire (SGW) and not using safety wire (NSGW). Patients, the data collecting physician, and the Statistical analyst; were concealed from the randomization process. Demographic factors were recorded for each participant. Patients were followed up for at least 1 month; registering intra-operative and post-operative complications. Results: From 2020 to 2021, 348 patients were randomized in two arms. Considering the lost cases during the study, 124 patients were finally analyzed in the SGW and 96 patients in the NSGW. Complications were not different between the two groups ( p > 0.05); though, operation time was significantly longer in the SGW group (31.7 min in SGW vs 28 min in NSGW p = 0.02) Conclusion: The safety guidewire seems to add no significant benefit to the TUL procedure outcomes in uncomplicated cases.