A. phagocytophilum is a tick-transmitted bacterium capable of infecting dogs, cats, horses, human beings and other species. Clinical observations of selected cases, as well as preliminary data from an experimental study, have suggested that doxycycline may not clear the infection in all treated dogs. Since differences in antibiotic susceptibility could occur between experimental strains and wild strains of this organism, this study evaluated the efficacy of doxycycline treatment for canine granulocytic anaplasmosis (CGA) in 11 naturally infected dogs. Dogs presenting signs compatible with CGA at two private clinics in the Northeastern United States were evaluated every 30 days over a 2-month period: at the initial consultation (day 0); after doxycycline treatment (day 30) and roughly 2 months after the initial consultation (day 60). Each enrolled dog was treated with doxycycline at a dose of 5 mg/kg twice a day for 28 days. Blood-EDTA and serum samples were collected at each evaluation date, and lymph node aspirates (LNA) were collected at days 0 and 60. Additionally, clients and veterinarians answered a clinical and epidemiological questionnaire at each visit. Finally, complete blood cell counts were performed from all enrolled dogs at each evaluation. DNA from blood-EDTA and LNA was extracted and A. phagocytophilum DNA was amplified targeting the msp2 gene. Antibodies against Anaplasma spp. were detected by Snap® 4Dx®. All 11 dogs were re-evaluated at the first follow-up (range of 24-47 days from day 0) and 10 dogs were evaluated for the second follow-up (range of 57-94 days). A. phagocytophilum DNA was not detected from blood-EDTA or LNA from any of the 11 dogs at day 30 nor from any of the 10 evaluated dogs at day 60. Six of 11 infected dogs seroconverted between day 0 and day 30, while 5 dogs were seroreactive on day 0. Platelet numbers significantly increased from day 0 to days 30 and 60 of the study (mean±SD: day 0 = 98.3 ± 69.3 x103/mm3, range 11-250 x103/mm3; day 30 = 255.7 ± 89.6 x103/mm3, range 147-420 x103/mm3; day 60 = 294.6 ± 92.3 x103/mm3, range 205-451 x103/mm3; p < 0.001). Body temperature significantly decreased after treatment (p < 0.001). After doxycycline treatment, all dogs fully recovered according to clients' assessment. Our results suggest that doxycycline is effective in controlling A. phagocytophilum infection and in reversing clinical signs in dogs in selected areas of the USA; however, a larger population should be evaluated to confirm these results.