We aimed to estimate the potential number of patients eligible for treatment with drotrecogin alfa (activated) when applying different international criteria. The study was a post-hoc analysis of inception cohort study of 691 patients with severe sepsis during 5878 consecutive intensive care unit admission episodes in 23 closed multi-disciplinary ICUs of 21 hospitals (16 tertiary and 5 university-affiliated) in Australia and New Zealand. Outcomes assessed were presence of contraindications to treatment with drotrecogin alfa (activated), an admission APACHE II score of 25 or greater and dysfunction of two or more organs. During 5878 consecutive intensive care admission episodes, 691 patients had severe sepsis, 553 (80.0%, 95% CI 77.0-83.0%) had no relative or absolute contraindication, 64 (9.3%, 7.1-11.4%) had a relative contraindication and 74 (10.7%, 8.4-13.0%) had an absolute contraindication. Two hundred and six patients (3.5%, 3.0-4.0%) had an APACHE II score of 25 or greater, 452 (7.7%, 7.0-8.4%) had dysfunction of two or more organs, 469 (8.0%, 7.3-8.7%) had either dysfunction of two or more organs or an APACHE II score of 25 or greater Relatively few patients had an absolute contraindication to treatment with drotrecogin alfa (activated). Selection based on the APACHE II score results in fewer eligible patients than selection based on multiple organ dysfunction. Depending on the selection criteria used, for every hundred admissions to intensive care, between 3.5 and 8.0 of patients may be eligible for treatment with drotrecogin alfa (activated).