Importance Most children and adolescents with kidney and ureteral stones are treated with ureteroscopy, despite the uncertainty and equal weight of guideline recommendations for ureteroscopy or shockwave lithotripsy. Objective To compare stone clearance and patient-reported outcomes among children and adolescents after ureteroscopy or shockwave lithotripsy. Design, Setting, and Participants This nonrandomized clinical trial enrolled patients between March 16, 2020, and July 31, 2023, at 31 medical centers in the US and Canada. Patients aged 8 to 21 years with kidney stones, ureteral stones, or both were included. Follow-up was completed on October 15, 2023. Interventions Ureteroscopy or shockwave lithotripsy. Main Outcomes and Measures The primary outcome was stone clearance assessed by standardized ultrasonography 6 (±2) weeks after surgery. Using inverse probability weighting and random intercepts for site, stone clearance was evaluated per kidney or ureter using logistic regression and estimated stone clearance rates were generated for each procedure. Results This study included 1142 patients (690 females 60.4%), with a median age of 15.6 years (IQR, 12.6-17.3 years). In terms of race and ethnicity, 41 patients (3.6%) were Black, 130 (11.4%) were Hispanic, and 884 (77.4%) were White. A total of 124 urologists treated 1069 and 197 kidneys or ureters with ureteroscopy and shockwave lithotripsy (n = 953 and n = 189 patients), respectively, with a median stone size of 6.0 mm (IQR, 4.0-9.0 mm). Ureteral stents were placed at time of index surgery for 841 procedures for 767 patients (80.4%) receiving ureteroscopy and for 6 procedures for 5 patients (2.6%) receiving shockwave lithotripsy. Stone clearance occurred in 474 patients who underwent ureteroscopy (71.2% 95% CI, 63.8%-78.5%) and in 105 patients who underwent shockwave lithotripsy (67.5% 95% CI, 61.0%-74.1%), a difference that was not statistically significant (risk difference, 3.6% 95% CI, −6.2% to 13.5%). Compared with shockwave lithotripsy, ureteroscopy resulted in greater pain interference (T-score difference, 5.0 95% CI, 2.3-7.8) and urinary symptoms (symptom score difference, 3.9 95% CI, 1.2-6.7) 1 week after surgery. Patients who had ureteroscopy missed more school (risk difference, 21.3% 95% CI, 9.7%-32.8%) and caregivers missed more work (risk difference, 23.0% 95% CI, 11.0%-35.0%) in the week after surgery. Conclusions and Relevance In this study of 1142 children and adolescents with kidney and ureteral stones, there was no clinically meaningful difference in stone clearance with ureteroscopy vs shockwave lithotripsy. Shockwave lithotripsy was associated with better patient-reported outcomes. These findings raise questions about the preference for ureteroscopy in practice. Trial Registration ClinicalTrials.gov Identifier: NCT04285658
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