To describe the clinical course of children with positive urine cultures without pyuria who were not given antibiotics initially, identify predictors of subsequent antibiotic treatment, and evaluate the association between subsequent treatment and urinary tract infection (UTI) within 30 days. We conducted a multicenter retrospective cohort study of children 1-24 months old who had positive urine cultures without pyuria and who were not started on antibiotics upon presentation to 3 healthcare systems from 2010-2021. Outcomes included clinical status at the time urine cultures resulted, escalation of care (emergency department visit or hospitalization) and subsequent antibiotic treatment within 7 days, and subsequent UTI within 30 days of presentation. Of 202 included children, 61% were female and median age was 9 months. Of 151 patients with clinical status information when cultures resulted, 107 (70.8%, 95% confidence interval [CI] 62.9-77.9%) were improved. Two of 202 children (1.0%, 95% CI 0.2-4.0%) experienced care escalation. Antibiotics were started in 142 (82.2%) children and treatment was associated with prior UTI (risk ratio [RR] 1.20, 95% CI 1.15-1.26) and lack of improvement (RR 1.22, 95% CI 1.13-1.33). Subsequent UTI was diagnosed in 2 of 164 (1.2%, 95% CI 0.1-4.3%) treated and 0 of 36 (0%, 95% CI 0-9.7%) untreated children. Seventy percent of children with positive urine cultures without pyuria improved before starting antibiotics, however >80% were ultimately treated. Future research should study the impact of diagnostic stewardship interventions and various urine testing strategies to optimize management of children evaluated for UTI. Seventy percent of children with positive urine cultures without pyuria improved before starting antibiotics, however >80% were ultimately treated. Future research should study the impact of diagnostic stewardship interventions to optimize management of children evaluated for UTI.