Objective: Limited evidence is available about long-term natural disease progression in hand osteoarthritis (HOA). The objective is to study natural radiographic and clinical disease progression in HOA after longer follow-up (i.e. 10 years) and to identify predictors for progression. Method: At baseline (T0), 270 patients with HOA were included in the Belgian HOA register. The majority (84.8%) was female and the mean age was 62.9 years. In total, 154 (57%) and 106 (39.3%) patients consented to follow-up after approximately 5 (T1) and 10 years (T2), respectively. Clinical and functional outcome measures were collected. Hand radiographs were taken and scored according to the anatomical phase scoring system. Results: At T2, most of the patients (73.3%) showed any radiographic progression compared to T0. Remodelling was most frequently seen and new erosive joints rather rarely. Functional Index for Hand Osteoarthritis (0-30) and Australian/Canadian Osteoarthritis Hand Index function (0-90) increased over time, from 8.8 to 9.9 (p = 0.017) and 39.3 to 41.9 (p = 0.035), respectively, after T2. Visual analogue scale pain (0-100) did not change (40.2 to 38.6 from T0 to T2, p = 0.656). Univariate and multivariate logistic regression retained baseline soft-tissue swelling [odds ratio (OR) 8.20 and 8.76, respectively], higher levels of pain (OR 4.08 and 4.30), and number of baseline erosive joints (OR 31.82 and 30.02) as significant predictors for radiographic progression. Conclusions: Significant radiographic progression is seen over time in HOA. While pain remains similar after 10 years, functional status declines. Patients with soft-tissue swelling, high levels of pain, and already erosive disease at baseline are prone to progression over time.