The factors predisposing to and complicating acute renal failure (ARF) in the medical intensive care unit (ICU), and their relative influence on outcome during ARF are unclear. We retrospectively evaluated the relative importance of age, prior chronic disease (including chronic renal failure), sepsis and organ system failure, for development and outcome of ARF in the medical ICU. Of 487 consecutively admitted patients, 78 (16%) had ARF, in 63% treated with renal replacement therapy. Mortality was 63%. Independently from each other, advancing age, prior chronic disease, and cardiovascular and pulmonary failure directly related to the development of ARF, while neurological failure related inversely. Sepsis only contributed to ARF prediction from these variables if cardiopulmonary failure was excluded. Advancing age, cardiovascular failure before and after onset of ARF, pulmonary failure before ARF and use of renal replacement therapy were the major independent factors directly related to ARF mortality, while prior chronic renal failure related inversely and sepsis did not contribute. Hence, the outcome of ARF in a medical ICU is largely dependent on factors predisposing to ARF, even though the severity and complications of ARF may partly contribute. Our results may help in deciding on the prevention and therapy of ARF in a medical ICU.