IMPORTANCE: Urinary tract infections are the most common infections in nursing home residents. However, most antibiotic use is for unlikely cystitis (ie, nonspecific symptoms and positive culture results secondary to asymptomatic bacteriuria or a urine sample improperly collected for culture) that is unnecessary and inappropriate. This antibiotic use is associated with an increased risk of antimicrobial resistance, adverse drug events, and Clostridioides difficile (formerly Clostridium difficile) infections. OBJECTIVE: To determine the association of a multifaceted antimicrobial stewardship and quality improvement intervention with the reduction in unnecessary antimicrobial use for unlikely cystitis among noncatheterized nursing home residents. DESIGN, SETTING, AND PARTICIPANTS: A quality improvement intervention evaluation was conducted to target antimicrobial use among residents with unlikely cystitis in 25 nursing homes across the United States. Baseline data were collected between February 1, 2017, and April 30, 2017. The intervention was conducted from May 1, 2017, to April 30, 2018. INTERVENTIONS: Intervention nursing homes (n = 12) were randomized to receive a 1-hour introductory webinar, pocket-sized educational cards, tools for system change, and educational clinical vignettes addressing the diagnosis and treatment of suspected uncomplicated cystitis. Monthly web-based coaching calls were held for staff of intervention nursing homes. All facilities received quarterly feedback reports regarding the management of uncomplicated cystitis. Control group nursing homes (n = 13) received usual care. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of antibiotic treatment for unlikely cystitis cases, defined using published criteria. Secondary outcomes included overall antibiotic use for any urinary tract infection and the safety outcomes of C difficile infections, as well as all-cause hospitalizations and death. RESULTS: Among the 25 nursing homes participating in this quality improvement study, including 512 408 intervention facility resident-days and 443 912 control facility resident-days, fewer unlikely cystitis cases were treated with antibiotics in intervention facilities compared with control facilities (adjusted incident rate ratio [AIRR], 0.73 [95% CI, 0.59-0.91]); C difficile infection rates were also lower in intervention nursing homes vs control nursing homes (AIRR, 0.35 [95% CI, 0.19-0.64]). Overall antibiotic use for any type of urinary tract infection was 17% lower in the intervention facilities than the control facilities (AIRR, 0.83 [95% CI, 0.70-0.99]; P = .04). There was no increase in all-cause hospitalizations or deaths due to the intervention (all-cause hospitalizations: AIRR, 0.95 [95% CI, 0.75-1.19]; all-cause death: AIRR, 0.92 [95% CI, 0.73-1.16]). CONCLUSIONS AND RELEVANCE: This study suggests that a low-intensity, multifaceted intervention was associated with improved antibiotic prescribing for uncomplicated cystitis in a cohort of nursing homes without an adverse association with other safety outcomes. Although promising, further study is needed to determine whether the intervention could be widely implemented to assist facilities in meeting new federal nursing home requirements for antimicrobial stewardship and quality assurance performance improvement programs.