Efficacy and safety of ceftriaxone (Oframax, Ranbaxy, India) in the treatment of 25 patients with Staphylococcus endocarditis (SE) were studied. The drug was administered intravenously in a dose of 2-4 g a day for 4 weeks and simultaneously gentamicin was used intramuscularly in a dose of 2-3 mg/kg body weight a day every 8 hours for 2 weeks. The treatment was followed by observation of the patients for up to 2 years under the hospital or dyspensary conditions. The disease was due to S. epidermidis (17 patients) or S.aureus (8 patients). The efficacy was controlled in the dynamics. The criteria of the therapy efficacy were disappearance of the disease clinical signs, normalization of the blood count and urinalysis and the pathogen eradication by the results of the control bacteriological blood analysis. The cure without any surgical correction was observed in 68 per cent of the patients and that with the valve replacement was stated in 24 per cent of the patients. The lethal outcome due to bacteriotoxic shock was recorded in 8 per cent of the patients. The SE relapsing was stated in 28 per cent of the patients 3 or more months after the ceftriaxone therapy completion. 10 patients (40 per cent) with evident clinicolaboratory improvement were discharged from the hospital 2 (4 patients) and 3 (6 patients) weeks after the therapy start for the treatment with ceftriaxone as outpatients. In 2 patients nausea as the adverse reaction was observed. Therefore, the complex clinicolaboratory investigation showed that the combined use of ceftriaxone and gentamicin was efficient and safe in the treatment of SE. Ceftriaxone may be considered as a basic drug for the therapy of SE. In some patients with SE the treatment with ceftriaxone may be completed under outpatient conditions.