The carriage of a characteristic sequence of amino acids at position 67-72 in the third hypervariable region of the HLA DRB1 chain has been linked to susceptibility to rheumatoid arthritis (RA). Whether this epitope is also a predictor of more severe disease remains controversial. Cartilage oligomeric matrix protein (COMP) is a protein, the serum levels of which have been found to correlate with large joint destructive disease in previous work. In this paper, we compare DRB1* typing and serum COMP levels in a prospectively observed group of RA patients with or without early hip joint destruction. The COMP levels at study inclusion, median 11 months from onset of symptoms, were significantly higher in the patients with early hip joint destruction compared to the patients in the more benign group. There was no difference in the number of disease susceptibility-related epitopes between the groups. DRB1*04, in contrast, was found among 8/8 patients with hip destruction, but also in 5/8 more benign cases. We conclude that in this type of RA patient, COMP serum levels are more informative predictors of aggressive disease than HLA DRB1* typing.