BACKGROUND: Urinary tract infections (UTI) are a disease of serious impact on every country in the world. Growing resistance has decreased the efficacy of many antimicrobial options. Aminoglycosides, like gentamicin, have long been used to treat gram-negative bacteria including UTIs. OBJECTIVES: The goal of this study was to compare single dose gentamicin to standard oral seven-day treatment in the emergency department for uncomplicated cases of acute uncomplicated cystitis in premenopausal women. METHODS: This was a randomized, open-label clinical trial of women at least 18 years of age, that were premenopausal, non-pregnant, with clinical signs of UTI and nitrite positive urine in the emergency department. Patients received either single-dose gentamicin or standard care for 7 days. Patients were contacted by telephone at 7 and 30 days and asked about clinical resolution of their UTI. The primary outcome of this study was symptom resolution at 7 days. RESULTS: Among those with 7-day telephonic follow-up, self-reported symptom resolution was 83.3% (25/30) among gentamicin treated patients and 48.1% (13/27) in the standard care group (X CONCLUSION: Single-dose gentamicin for acute uncomplicated cystitis in premenopausal, nitrite positive women was an appropriate UTI treatment and more effective than standard care for symptom resolution at 7-days in our patient population. This strategy has the potential to revolutionize treatment by offering an antibiotic with high sensitivities, high efficacy, simple administration in many different healthcare settings, 100% compliance, and increased patient satisfaction for acute cystitis treatment.