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Aim: Routine practice in the ICU of University College London (UCL) Hospitals is to use short course (5-6 days) monotherapy, unless contraindicated (e.g. endocarditis, osteomyelitis). The aim of this study is to assess our policy by monitoring the clinical response, relapse rate and patient outcome., Methods: A prospective observational study was carried out from February to July 2000. Clinically significant bacteraemia was identified by daily prospective surveillance of all positive blood cultures. On all the patients we recorded: 1) demographics; 2) antibiotic therapy (type, duration) and ACCP/SCCM sepsis criteria; 3) ICU support techniques (e.g. mechanical ventilation, intravascular catheter changes); 4) development of further bacteraemia or relapses. For all positive results, Gram stain, identification and antibiotic sensitivity patterns were noted. SPSS software was used for statistical analyses., Results: Out of 713 admitted to the ICU over the study period, 84 (8.2%) patients experienced 102 bacteraemic episodes: 14 community-, 28 hospital- and 60 ICU-acquired (occurring in 49 patients). A total of 78 (76.4%) episodes [8 (57%) community-, 22 (79%) hospital- and 48 (80%) ICU-acquired] were treated with short course monotherapy. Moreover a low rate (23.8%) of death directly related to the bacteraemia and a satisfactory (72%) clinical response were recorded. ICU-acquired multidrug resistant Gram-negative bacteraemias (6.5%) and fungaemias (3%) were also uncommon. No patient discharged from the ICU, subsequently developed either bacteraemia relapse, or any long-term related complication., Conclusions: Short course antibiotic monotherapy strategy appears to provide a satisfactory clinical response, low relapse rate and no long-term infectious complications. Multicentre studies are warranted to confirm the efficacy of our practice.