During a population survey in 1975–1978 persons with radiological osteoarthritis (ROA) of the knee were identified. After 12 years a follow-up study was conducted to study the effect of circulating insulin-like growth factor-1 (IGF-1) on cartilage loss, osteophyte growth and overall progression in 141 persons with confirmed ROA of the knee. The outcome measures were scored by comparing the radiographs taken at baseline and at follow-up. Insulin-like growth factor-1 was measured by radioimmunoassay in serum taken at follow-up and in 79% of the baseline sera. After adjusting for age, gender and body mass index at baseline, IGF-1 concentration at follow-up was related to osteophyte growth and overall progression. The adjusted odds ratio of the highest vs the lowest tertile was 2.96 (95% Cl: 1.15–7.60) for osteophyte growth and 2.58 (1.01–6.60) for overall progression. No clear relationship was found with cartilage loss. These results were confirmed when baseline IGF-1 was studied. We conclude that the circulating IGF-1 concentration has an effect on the course of knee OA by influencing osteophyte formation but a preventive effect on cartilage loss could not be shown.