This prospective, non-randomized trial, compared the efficacy and tolerance of a doxycycline-rifampin regimen, administered for 45 days, versus doxycycline-rifampin given for 45 days plus gentamicin for the first 7-10 days, in the treatment of human brucellosis. Of 238 patients that were initially included in the study, 181 were finally evaluated. Ninety-four were treated with the doxycycline-rifampin and 87 with the doxycycline-rifampin-gentamicin regimens. In the doxycycline-rifampin group: relapses were noted in 13 (13.8%) patients; therapeutic failures in five (5.3%); and mild adverse effects in 28 (29.8%). In the doxycycline-rifampin-gentamicin group: four (4.6%) relapsed; and five (5.7%) therapeutic failures were registered. Mild adverse effects were registered in 29 (33.3%) patients. The doxycycline-rifampin-gentamicin regimen demonstrated a significantly lower relapse rate compared to the doxycycline-rifampin combination (P = 0.034). We conclude that adding gentamicin for the first 7-10 days to the standard oral doxycycline-rifampin regimen can decrease the rate of relapses.