To date, anaesthesia‐related mortality, morbidity and risk factors have almost exclusively been studied qualitatively rather than quantitatively. Therefore, knowledge of the relative risk associated with many anaesthesia‐related factors is still lacking. Recently, a quantitative study of the determinants and prevention of morbidity and mortality in anaesthesia was started in the Netherlands. Its objective is to study severe peri‐operative morbidity and mortality as a function of anaesthesia‐related risk factors. The study is designed as a case‐control study within a prospectively defined cohort. The cohort comprises all patients undergoing an anaesthetic procedure, either general, regional or a combination, in one of 61 hospitals between 1 January 1995 and 1 January 1997. A ‘case’ is a patient who dies within 24 h of undergoing an anaesthetic procedure or who remains comatose 24 h after an anaesthetic procedure. A ‘control’ patient is a randomly chosen patient who has undergone anaesthesia and is matched for gender and age. The present report discusses the study protocol.