Long term management of women with uncomplicated recurrent urinary tract infection (UTI) is challenging. Although continuous antibiotic prophylaxis is a common form of management, its use is recommended generally for no longer than 12 months. We aimed to evaluate antibiotic resistance and tolerability in women with recurrent UTI treated with “prolonged” continuous antibiotic prophylaxis, defined as longer than 12 months. A retrospective query was performed to identify adult women referred to TTUHSC-EP Urogynecology clinic with uncomplicated recurrent UTI from 1/1/2014-12/31/2018. Recurrent UTI was defined as ≥2 symptomatic UTIs in a 6-month period or ≥3 in a 12-month period. Exclusion criteria included symptomatic prolapse, pelvic malignancy, urinary retention, voiding dysfunction with prior incontinence surgery and active pregnancy. Demographic and clinical data, including strategy and duration of treatment, was recorded for initial and subsequent clinic visits, until present time. "Resistance” was defined as resistance to prophylactic antibiotic as per urine culture in a symptomatic UTI during the prophylaxis course. Descriptive statistics were calculated. Two sample t-tests and Chi square were used for between-group comparisons. Multiple logistic regression was performed to evaluate antibiotic resistance between different duration of antibiotic prophylaxis. One hundred and eighty four women met inclusion criteria. Mean age was 62.1 ± 16. Total follow up time from initial visit was 60.3 ± 59.4 weeks. Initial strategies for prophylaxis included daily or intermittent antibiotics (60.8%), vaginal estrogen (45%), D-mannose (2.6%) and cranberry (1.5%) supplements, alone or in combination. Eventually, most patients were started on continuous antibiotic prophylaxis (84%). Twenty-seven percent (N=42) of those on continuous antibiotic prophylaxis had a “prolonged” duration. Resistance to prophylactic antibiotic occurred in 19.1% of those on "prolonged” courses vs. 5.3% of those on courses of ≦12 months (OR 3.7, 95%CI 1.14-12.18, p=0.03). For those on “prolonged” antibiotic prophylaxis, time to antibiotic resistance was 136.5 ± 92.8 weeks. On regression, factors including age, parity, prior incontinence surgery and prolapse stage did not significantly increase risk for resistance, with exception of thyroid disease (OR 4.8 95%CI 1.43-16.01, p=0.01). There were no cases of discontinuation of continuous prophylaxis due to abnormalities in liver or renal function, or intolerance to antibiotic. In women with recurrent UTI, continuous antibiotic prophylaxis longer than 12 months was associated with an almost four-fold increased risk for resistance to the prophylactic antibiotic. However, the mean time for resistance was ≧2.5 years, and prophylaxis was well tolerated. Prolonged antibiotic prophylaxis seems acceptable with appropriate monitoring and counseling on the risk of resistance.