We conducted a prospective, randomized, open-label trial to evaluate the efficacy and tolerability of cefepime in the treatment of osteomyelitis caused by Gram-negative bacilli. Hospitalized patients with diagnosis of osteomyelitis due to Gram-negative bacilli susceptible to cefepime were elegible for enrollment. Cefepime was administered intravenously or intramuscularly (2 g every 8 or 12 hours). Microorganisms were considered susceptible to cefepime when the MIC was <8 mg/l. Forty-five patients with bone infections were enrolled, forty-three with osteomyelitis (22 chronic and 21 acute) and two with arthritis. In the per protocol analysis 42 patients were evaluated: 30 (71.4%) were cured. In the intent to treat analysis 45 patients were evaluated: 33 (73.3%) were cured. Our trial suggests that cefepime is as effective as other modern parenteral beta-lactam antibiotics in the treatment of osteomyelitis due to Gram-negative bacilli.