Nitrofurantoin remains a key oral antibiotic stewardship program (ASP) option in the treatment of acute uncomplicated cystitis (AUC) due to multi-drug resistant (MDR) Gram negative bacilli (GNB). However, there have been concerns regarding decreased nitrofurantoin efficacy with renal insufficiency. In our experience over the past three decades, nitrofurantoin has been safe and effective in treating AUC in hospitalized adults with renal insufficiency. Accordingly, we retrospectively reviewed our recent experience treating AUC in hospitalized adults with decreased renal function (CrCl < 60 ml/min) with nitrofurantoin. Excluded were complicated urinary tract infections. Urinary isolated susceptibility testing was done by micro broth dilution (MBD). Treatment duration was 5-7 days. Cure was defined as eradication of the uropathogen and failure was defined as minimal/no decrease in urine colony counts. Of 26 evaluable patients with renal insufficiency (CrCl < 60 ml/min), nitrofurantoin eradicated the uropathogen in 18/26 (69%) of patients, and failed in 8/26 (31%). Of the eight failures, five were due to intrinsically resistant uropathogens, e.g., Proteus sp., and one failure was related to an alkaline urine. Of the treatment failures, only two were due to renal insufficiency, i.e., CrCl < 30 ml/min. Since there are few oral antibiotics available to treat AUC due to MDR GNB uropathogens, these results have important ASP implications. Currently, nitfurantoin is not recommended if CrCl < 60 ml/min. In our experience, used appropriately against susceptible uropathogens, nitrofurantoin was highly effective in nearly all patients with CrCl = 30-60 ml/min., and only failed in two patients due to renal insufficiency (CrCl < 30 ml/ml).