Hospitalized patients with asymptomatic bacteriuria (ASB) often receive unnecessary antibiotic treatment, which increases antibiotic resistance and adverse events. To determine whether diagnostic stewardship (avoiding unnecessary urine cultures) or antibiotic stewardship (reducing unnecessary antibiotic treatment after an unnecessary culture) is associated with better outcomes in reducing antibiotic use for ASB. This 3-year, prospective quality improvement study included hospitalized general care medicine patients with a positive urine culture among 46 hospitals participating in a collaborative quality initiative, the Michigan Hospital Medicine Safety Consortium. Data were collected from July 1, 2017, through March 31, 2020, and analyzed from February to October 2022. Participation in the Michigan Hospital Medicine Safety Consortium with antibiotic and diagnostic stewardship strategies at hospital discretion. Overall improvement in ASB-related antibiotic use was estimated as change in percentage of patients treated with antibiotics who had ASB. Effect of diagnostic stewardship was estimated as change in percentage of patients with a positive urine culture who had ASB. Effect of antibiotic stewardship was estimated as change in percentage of patients with ASB who received antibiotics and antibiotic duration. Of the 14 572 patients with a positive urine culture included in the study (median [IQR] age, 75.8 [64.2-85.1] years; 70.5% female); 28.4% (n = 4134) had ASB, of whom 76.8% (n = 3175) received antibiotics. Over the study period, the percentage of patients treated with antibiotics who had ASB (overall ASB-related antibiotic use) declined from 29.1% (95% CI, 26.2%-32.2%) to 17.1% (95% CI, 14.3%-20.2%) (adjusted odds ratio [aOR], 0.94 per quarter; 95% CI, 0.92-0.96). The percentage of patients with a positive urine culture who had ASB (diagnostic stewardship metric) declined from 34.1% (95% CI, 31.0%-37.3%) to 22.5% (95% CI, 19.7%-25.6%) (aOR, 0.95 per quarter; 95% CI, 0.93-0.97). The percentage of patients with ASB who received antibiotics (antibiotic stewardship metric) remained stable, from 82.0% (95% CI, 77.7%-85.6%) to 76.3% (95% CI, 68.5%-82.6%) (aOR, 0.97 per quarter; 95% CI, 0.94-1.01), as did adjusted mean antibiotic duration, from 6.38 (95% CI, 6.00-6.78) days to 5.93 (95% CI, 5.54-6.35) days (adjusted incidence rate ratio, 0.99 per quarter; 95% CI, 0.99-1.00). This quality improvement study showed that over 3 years, ASB-related antibiotic use decreased and was associated with a decline in unnecessary urine cultures. Hospitals should prioritize reducing unnecessary urine cultures (ie, diagnostic stewardship) to reduce antibiotic treatment related to ASB.