Objective: To investigate whether offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis (OA) have an increased risk of worsening knee pain over 8 years as compared with controls with no family history of knee OA. Methods: A total of 219 participants (mean age 48 years, range 29-61 years) with 115 offspring and 104 controls participated in this study. Knee pain was respectively assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 2 years and 10 years. T1-weighted or T2-weighted fat saturated MRI of the right knee was performed to assess knee cartilage defects, bone marrow lesions, effusion, meniscal extrusion and tears. Results: Compared with controls, the prevalence of knee pain for offspring was similar at 2 years (56% vs 54%, p=0.764) and higher at 10 years (74% vs 54%, p=0.002). Over 8 years, offspring more frequently had an increase in total knee pain (66% vs 41% ≥1 point increase, p=0.003) and in all subscales apart from walking (all p<0.05). In multivariable analysis, after adjustment for confounders and structural factors, offspring had an elevated risk of worsening total knee pain (OR=2.16, 95% CI 1.14 to 4.12), as well as each subscale except for walking and standing (OR=1.95 to 3.30, all p<0.05). Conclusions: Offspring with a family history of knee OA have an increased risk of worsening knee pain, which is independent of structural factors, suggesting that genetic factors may be involved in the pathogenesis of knee pain.