Thrombocytosis is common in iron deficiency and resolves following iron repletion. Increased platelet number, whether from iron deficiency or from other causes, may increase the risk of thrombovascular events. One mechanism thought to mediate iron deficiency-induced thrombocytosis is increased erythropoietin production. Similarly, erythropoietic stimulating agents (ESA) have long been known to increase platelet number and frequently lead to functional or absolute iron deficiency. This state of relative or absolute iron deficiency may be the mechanism whereby ESA increase the platelet count. If correct, co-administration of iron should prevent or diminish ESA-driven thrombocytosis. Data from the DRIVE trial in hemodialysis patients do, in fact, suggest that this is the case. Platelet counts in patients receiving IV iron decreased, while they remained unchanged in patients not given iron (mean change -29,000/μl vs. -0/μl; p = 0.017). Other supporting data have been observed in IV iron trials in oncology patients. The harm from higher hemoglobin targets and higher ESA doses may be mediated in part through induction of iron deficiency and thrombocytosis. The major anemia trials of ESAs have not reported platelet data, but should examine the relationship of platelet count, iron deficiency, IV iron administration, and cardiovascular events in greater detail.