Objective. Joint bleeding, or hemarthrosis, leads in time to severe joint damage. This study was carried out to test the in vitro thresholds of exposure time and concentration that lead to irreversible joint damage, to add to the discussion on the usefulness of aspiration of the joint after a hemorrhage. Methods. Explants of healthy human articular cartilage tissue were cultured in the presence or absence of 50% (volume/volume) blood for 1, 2, 3, or 4 days or in the presence of 0%, 5%, 10%, 20%, 30%, or 50% (v/v) blood for 4 days, followed by a 12-day period of recovery after withdrawal of blood. The effect of blood exposure on cartilage was determined by measuring the rate of proteoglycan synthesis as well as the release and content of cartilage matrix proteoglycans and the activity of matrix metalloproteinases. Results. Exposure of cartilage to 50% (v/v) blood led to adverse changes that were largely independent of the exposure time. The adverse effects persisted after an initial exposure of up to or exceeding 2 days. Exposure of cartilage to increasing concentrations of blood for 4 days led to concentration-dependent adverse changes. These effects persisted when the concentration equaled or exceeded 10% (v/v) blood. Moreover, after 2 days of exposure to a blood load of 10% (v/v), the adverse effects on cartilage were not reversible. Conclusion. A 2-day exposure of cartilage in vitro to 10% (v/v) blood leads to prolonged impairment of joint cartilage. This suggests that aspiration of blood from the joint within 2 days after hemarthrosis should be considered to prevent blood-induced joint damage in the long term. © 2007, American College of Rheumatology.