Objectives Osteoarthritis is a leading cause of immobility and joint replacement, two strong risk factors for venous thromboembolism (VTE). We aimed to examine the relation of knee, hip and hand osteoarthritis to the risk of VTE and investigate joint replacement as a potential mediator. Methods We conducted three cohort studies using data from The Health Improvement Network. Up to five individuals without osteoarthritis were matched to each case of incident knee (n=20 696), hip (n=10 411) or hand (n=6329) osteoarthritis by age, sex, entry time and body mass index. We examined the relation of osteoarthritis to VTE (pulmonary embolism and deep vein thrombosis) using a multivariable Cox proportional hazard model. Results VTE developed in 327 individuals with knee osteoarthritis and 951 individuals without osteoarthritis (2.7 vs 2.0 per 1000 person-years), with multivariable-Adjusted HR being 1.38 (95% CI 1.23 to 1.56). The indirect effect (HR) of knee osteoarthritis on VTE through knee replacement was 1.07 (95% CI 1.01 to 1.15), explaining 24.8% of its total effect on VTE. Risk of VTE was higher in hip osteoarthritis than non-osteoarthritis (3.3 vs 1.8 per 1000 person-years; multivariable-Adjusted HR=1.83, 95% CI 1.56 to 2.13). The indirect effect through hip replacement yielded an HR of 1.14 (95% CI 1.04 to 1.25), explaining 28.1% of the total effect. No statistically significant difference in VTE risk was observed between hand osteoarthritis and non-osteoarthritis (1.5 vs 1.6 per 1000 person-years; multivariable-Adjusted HR=0.88, 95% CI 0.67 to 1.16). Conclusion Our large population-based cohort study provides the first evidence that knee or hip osteoarthritis, but not hand osteoarthritis, was associated with an increased risk of VTE, and such an association was partially mediated through knee or hip replacement.