Background: Cephalosporins are increasingly used to treat severe urinary tract infections (sUTI) due to rising resistance with standard antibioics. When switching from intravenous to oral cephalosporins there is limited clinical outcome data to guide selection. Objective: To compare the failure rate between cephalexin and cefdinir when used as oral step-down therapy in sUTI. Methods: In this retrospective study, we assessed patients admitted to 3 hospitals for sUTI over a 1-year period. Cases were identified using ICD-10 codes N10, N39.0, and A41.9. Patients who received intravenous antibiotics for >24 hours and completed treatment with cephalexin or cefdinir were included. The primary composite outcome was death, rehospitalization for UTI in 30 days, unplanned clinic or emergency visit for UTI in 30 days, hospitalization for any reason in 90 days, or Clostridoides difficile infection. Secondary outcomes included each individual composite outcome element. Results: Overall, 75 cefdinir and 135 cephalexin cases were included. Patients were similar in baseline characteristics. Pyelonephritis occurred among the cephalexin group (30.2% vs 46.7%, P = 0.024). Composite failure occurred in 8% of patients receiving cefdinir and 14.1% receiving cephalexin (P = 0.193). Secondary outcomes did not differ except clinic or emergency visit for UTI was lower among patients receiving cefdinir than cephalexin (0% vs 7.2%; P = 0.028). Logistic regression revealed no significant variable associations with treatment failure, except for cephalexin use, which was associated with clinic or emergency visit for UTI (r2 = 0.075). Conclusions: Treatment failure rates did not differ between cefdinir and cephalexin; however, patients receiving cephalexin had more unplanned clinic and emergency visits.