Acute pyelonephritis is a clinical syndrome that can be confused with other conditions. To investigate this problem, a retrospective cohort study was conducted using two mutually exclusive sets of clinical criteria for acute pyelonephritis in women 15 years of age or older who presented to the emergency department of a university hospital. All patients had pyuria, and one group had documented fever (temperature of > or = 37.8 degrees C) while the other group had a temperature of < 37.8 degrees C but had other evidence of possible upper tract infection. The study cohort was comprised of 103 febrile and 201 afebrile patients. Afebrile hospitalized patients were ultimately found to have another diagnosis more often than were the febrile hospitalized patients (35% v 7%; P = .02), and the afebrile nonhospitalized patients were more likely to have another diagnosis than were the febrile nonhospitalized patients (13% v 0%; P = .004). Other diagnoses included cholecystitis, pelvic inflammatory disease, and diverticulitis. The positive predictive value of the definition of pyelonephritis in the febrile group was 0.98, and it was 0.84 for the afebrile group. Physicians examining patients with clinical evidence of acute pyelonephritis but without objective fever should be alert for alternative diagnoses.