Introduction: Cardiovascular (CV) mortality is increased in patients with ankylosing spondylitis (AS), but little is known about CV morbidity beyond the fact that they have a two-fold higher prevalence of ischemic heart disease than controls due to the inflammatory pattern of the disease itself, and a higher prevalence of traditional CV risk factors than the general population. Anti-TNF drugs reduce inflammation and a number of studies have reported a reduction in sub-clinical atherosclerosis in AS patients treated with anti-TNF drugs, thus suggesting that inflammation contributes to their higher CV risk. Anti-TNF drugs also alter the lipid profiles of AS patients, although these changes may reflect their normalization secondary to inflammation control, and improve their other myocardial alterations. Areas covered: This review concentrates on the risk of cardiovascular morbidity and mortality among AS patients and the effect of anti-TNF drugs on this risk, with particular emphasis on the putative causes involved and the aspects that are relevant in clinical practice. Expert opinion: The growing evidence of CV disease in AS means that all clinicians need to know how to prevent it and treat patients appropriately. It is important to bear in mind the EULAR guidelines, which state that a rheumatologist is responsible for monitoring all AS patients for signs of CV involvement because this is essential in order to ensure that they are treated properly. As there is little clinical evidence concerning the effects of biological drugs other than anti-TNF agents, treatment should be decided on the basis of the clinical aspects of the type of AS and the CV co-morbidity: for example, patients who are hypertensive or dyslipidemic should immediately start treatment with an anti-hypertensive agent and/or a statin. All of the patients should be educated to prevent CV events by keeping to a balanced healthy diet, avoiding tobacco smoking, and maintaining normal blood pressure, LDL-cholesterol and glucose levels. Finally, all clinicians (but particularly rheumatologists) should always bear in mind CV complications in order to guarantee that the quality of life of AS patients is as good as possible.