Introduction Iron is an essential nutrient for living cells because of its role as a cofactor for enzymes in the mitochondrial respiration chain, in the DNA synthesis, and being the central molecule for binding and transport of oxygen by hemoglobin and myoglobin. 1 7 This review will analyze, from a clinical and pathogenic point of view, the existing literature data on the relationship between iron and arterial and venous thrombosis. Iron deficiency and thrombosis 8 26 27 28 29 9 26 13 30 31 32 27 33 34 35 36 37 23 13 26 13 38 1 13 39 40 Iron overload and thrombosis 7 41 44 41 dl 42 44 45 47 48 53 54 55 56 57 7 58 72 61 65 64 71 60 61 69 70 72 61 HFE HFE 73 88 75 77 75 76 77 78 61 79 89 61 80 81 HFE 86 HFE 89 79 90 94 95 1 Table 1 Summary of the most important studies on the association between HFE gene mutations (C282Y and H63D) and the risk of cardiovascular diseases Authors [reference] Study design Population Results 75 Prospective 1,150 individuals C282Y heterozygosity is associated with a 2.3 RR for AMI compared with noncarriers 76 Prospective 12,239 postmenopausal women C282Y heterozygosity is associated with a 1.6 RR for TCD compared with noncarriers 77 Prospective 243 CHD cases and 535 controls C282Y heterozygosity is associated with a 2.7 RR for CHT compared with noncarriers 78 Case–control 41 C282Y/C282Y cases and 51 controls C282Y homozygosity is associated with impaired endothelial function 61 Case–control 546 CHD cases and 303 controls C282Y mutation is not associated with CHD 80 Case–control 1,098 subjects C282Y mutation is not a risk factor for asymptomatic carotid atherosclerosis 81 Case–control 256 CHD cases and 272 controls C282Y and H63D mutations are not associated with CHD 79 Prospective 9,178 individuals C282Y and H63D mutations are not associated with CHD Case–control 2,441 CHD and 1,113 AMI cases vs 8,080 controls C282Y and H63D mutations are not associated with CHD 86 Case–control 482 CHD cases and 1,104 controls C282Y mutation is not associated with CHD 88 Case–control 924 AMI cases and 1,029 controls C282Y mutation is not associated with CHD 89 Case–control 907 individuals HFE genotype is not related to brachial endothelial function and carotid atherosclerosis AMI CHD RR TCD Conclusions It is interesting to note that although with different pathogenic mechanisms, both iron deficiency and overload have been associated with an increased thrombotic risk in experimental and clinical studies. However, several aspects need to be still elucidated in this field. In particular, large prospective controlled trials are needed to elucidate the role of genetic markers of iron stores and the impact of long-term iron depletion on morbidity and mortality from cardiovascular events.