The 2011 Infectious Diseases Society of America guidelines for treatment of uncomplicated urinary tract infections (UTIs) recommend non-β-lactam antibiotics for empiric therapy. However, increasing Escherichia coli and Klebsiella spp. resistance to first-line antibiotic therapies has necessitated the need for alternative agents. Based on local antibiogram data, cephalexin has become the preferred oral antibiotic for empiric treatment of UTIs at our institution. The purpose of this single-center retrospective review was to assess clinical outcomes of patients discharged from the emergency department (ED) who received cephalexin for the treatment of uncomplicated UTIs. The primary outcome of this study was to assess the proportion of patients with clinical success 30 days after discharge from the ED. Patients were excluded if they were <18 years of age, received ≥10 days of cephalexin, received antibiotics for any indication other than uncomplicated UTI, received antibiotics within 60 days of their ED visit, or had structural abnormalities. A total of 264 patients were included for evaluation, and 214 patients (81.1%) met the criteria for clinical success. Overall, 28 (10.6%) patients required a change in antibiotics based on cultures and sensitivities, 18 (6.8%) patients returned for nonresolving or worsening symptoms, and 4 (1.5%) patients required both a change in antibiotics and returned for nonresolving or worsening symptoms. Short courses of twice-daily cephalexin appear to be a safe and effective option for the empiric treatment of uncomplicated UTIs.