Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects about 1% of the adult population. RA sufferers not only have a high chronic disease burden, but may also experience increased cardiovascular disease (CVD) and mortality as the prevalence of myocardial infarction (MI) is 4 times higher in RA patients than in general population, and there is ample evidence showing that coagulation processes are active in RA. Fibrin accumulation in the synovium is one of the most striking pathological features of rheumatoid synovitis and characteristic RA antibodies such as anti-citrullinated protein antibodies (ACPA) can cross-react with epitopes exposed on fibrin and fibrinogen molecules, and thus impair fibrinolysis. The inflammation, coagulation and fibrinolytic systems are modulated by a common mechanism that includes the involvement of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6). It has long been recognised that extensive cross-talk takes place between the coagulation pathway and the inflammatory process at various levels, and there is growing evidence that this interaction may be relevant to arthritis. Large-scale, long-term studies have shown that anti-TNF-α treatment improves the clinical and laboratory measures of disease activity, and reduces local and systemic inflammation. TNF-α blockade may therefore also reduce the impaired coagulation and cardiovascular risk associated with RA. This review provides an overview of the pathophysiological role of TNF-α in thrombotic mechanisms and the evidence so far available indicating that anti-TNF-α treatment can modify cardiovascular risk in RA.