Abstract Background This study measured the magnitude and determinants of clinical and radiological progression in patients with hand osteoarthritis (HOA) over a 2-year prospective follow-up to gain a greater understanding of the disease time course. Methods Two hundred three consecutive outpatients diagnosed with HOA were followed for 2 years (183 women, median age 69 years). Pain and function were evaluated using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), and clinical examination recorded the number of painful/swollen joints and nodes. X-rays were scored using Kellgren-Lawrence (KL) and Verbruggen-Veys scales. Clinical progression was defined as deterioration in AUSCAN ≥ the minimal clinically important difference. Radiographic progression was defined as (a) one new erosive/remodeled joint, (b) progression of ≥ one anatomical stage in one joint, or (c) change in KL total score above the smallest detectable difference. Logistic regression was performed to determine whether patient characteristics influenced clinical and radiological progression. Results After 2 years, all radiographic scores deteriorated significantly in the study population (p