To evaluate the prognostic significance of lupus anticoagulant (LA), 37 SLE patients with LA and 37 age- and sex-matched SLE patients without LA were followed up for a median of 22 years, of which 16 years (median) after the initial LA-testing. Deep venous thrombosis was observed in 20 (54%) patients with LA. Of these patients, 90% had the first episode within 8 years after the onset of SLE symptoms, as compared to only one of the six LA-negative patients with deep venous thrombosis (P 0.0001). Cerebral artery occlusions were more common in patients with LA (P 0.016), but typically appeared as a late phenomenon. Nephritis or neuropsychiatric manifestations, previously associated with a poor outcome in SLE, did not correlate with the presence of LA. However, higher mortality was associated with both LA (P 0.021) and a history of deep venous thrombosis (P 0.004), as well as with nephritis (P 0.038). The most common cause of death in both LA positives and negatives was vascular occlusion. In conclusion, it appears that the first episode of deep venous thrombosis in patients with LA is typically seen early in the course of disease, and that LA and a history of deep venous thrombosis are both associated with increased mortality.