Human ehrlichiosis is a serious disease that can be fatal if not treated appropriately. We examined patients with a clinical presentation consistent with the syndrome of ehrlichiosis and a positive blood polymerase chain reaction (PCR) test for all known Ehrlichia species or Anaplasma phagocytophilum admitted to Barnes-Jewish Hospital in St. Louis, MO, from 1996 to 2006. Patients who had doxycycline initiated within the first 24 hours of admission to the hospital were compared with patients who did not have empiric doxycycline therapy.A total of 46 patients had a positive blood PCR test for Ehrlichia or Anaplasma phagocytophilum, and 28 (60.9%) had a delay in doxycycline therapy. At presentation, patients with a delay in therapy were more likely to present with an abnormal lung exam and altered mental status. None of the patients experiencing a delay in doxycycline treatment had the diagnosis of ehrlichiosis documented at the time of hospital admission, compared with 13 (72.2%) of the patients who were treated empirically (p < 0.001).Patients not started on doxycycline at hospital admission had a significantly increased rate of transfer to the intensive care unit (39.3% vs. 0%; p < 0.001) and requirement for mechanical ventilation (28.6% vs. 0%; p < 0.001). Patients with a treatment delay also had a longer hospital stay (12.3 ± 11 d vs. 3.9 ± 1.9 d, respectively; p < 0.001) and a longer length of illness (20.9 ± 14.2 d vs. 8.9 ± 2.7 d, respectively; p = 0.001).These data suggest that clinicians living in an area where Ehrlichia is endemic should have a high suspicion for ehrlichiosis, and a low threshold for instituting empiric antibiotic therapy with doxycycline.