OBJECTIVE: To evaluate the risk of future hip or knee osteoarthritis (OA) in subjects with hand OA at baseline and to evaluate whether the concurrent presence of hand OA, other risk factors for OA, or an OA biomarker (type II collagen C-telopeptide degradation product [CTX-II]) further increases the risk. METHODS: Radiographs of the hands (baseline) and the hips and knees (baseline and 6.6 years later) were obtained in a randomly selected subset of participants in the Rotterdam Study who were ages 55 years and older. Radiographs were scored for the presence of OA using the Kellgren/Lawrence (K/L) system. A total of 1,235 subjects without OA of the hip/knee (K/L score 0-1) at baseline were included in the study. CTX-II levels were measured at baseline. The independent risk of future hip/knee OA in subjects with hand OA at baseline was assessed by logistic regression, as stratified for age, sex, body mass index, family history of OA, and heavy workload. RESULTS: Overall 12.1% of the participants (19.7% of those with hand OA versus 10.0% of those without) developed hip or knee OA (odds ratio [OR] 2.1 [95% confidence interval (95% CI) 1.3-3.1]). Subjects with hand OA had an increased risk of future hip OA (OR 3.0 [95% CI 1.6-5.4]), which was further increased in those with a family history of OA. Subjects with hand OA had an OR of 1.6 [95% CI 1.0-2.8) for the future development of knee OA, which was further increased in those who were overweight. Concurrent hand OA and high levels of CTX-II further increased the risk of having hip or knee OA at followup (OR 4.2 [95% CI 2.3-7.8]). CONCLUSION: The presence of hand OA at baseline showed an increased risk of future hip/knee OA (higher for hip OA than for knee OA). The concurrent presence of hand OA and other OA risk factors or high CTX-II levels further increased the risk of future hip/knee OA.