This study reviews the outcome of patients with uncomplicated catheter-related Staphylococcus aureus bacteremia diagnosed in our hospital from January 1997 to December 1999 and treated with short-course antibiotic therapy. Our aim was to assess the effectiveness of this regimen for minimizing complications (relapses, endocarditis and metastatic foci). A total of 213 episodes of bacteremia were registered and 167 (78.4%) were nosocomial. Among these, 87 (52.1%) were catheter-related Staphylococcus aureus bacteremia and 20 were primary nosocomial bacteremia. Endocarditis was diagnosed during the acute episode in 7/107 of these patients (2 by persistent fever after catheter removal and 5 by metastatic foci; 3 of them also had cardiac risk factors) and confirmed with transesophageal echocardiography. Among the 84/87 catheter-related Staphylococcus aureus bacteremia and 16/20 primary nosocomial bacteremia patients who did not develop endocarditis, 31 patients died during the acute episode (16 due to sepsis despite initiation of antibiotic treatment and 15 due to the underlying disease) and five had osteoarticular foci. The remaining 64 episodes were considered to be uncomplicated bacteremia (no cardiac risk factors, persistent fever, metastatic foci, or clinical signs of endocarditis) and were treated with 10-14 days of high-dose antistaphylococcal antibiotics. Echocardiography was not mandatory in these patients. Of the 64 uncomplicated episodes, 62 were followed for at least 3 months and none relapsed or developed endocarditis. Even though some of the patients might have had subclinical endocarditis, short-course therapy with high doses of antistaphylococcal antibiotics was effective for treating uncomplicated catheter-related Staphylococcus aureus bacteremia. Transesophageal echocardiography may not be necessary in these cases.