Hospital-acquired anemia (HAA) is common, often develops in the absence of bleeding, and is associated with poor outcomes in patients with acute myocardial infarction (AMI). It is unknown whether red cell distribution width (RDW) and mean corpuscular volume (MCV), which are routinely available markers of iron deficiency, are associated with development of HAA during AMI. We studied 15,133 patients with AMI without anemia at admission. HAA was defined by nadir hemoglobin levels below age-, gender-, and race-specific thresholds and moderatesevere HAA was defined as nadir hemoglobin ≤11 g/dl. We examined the association between low MCV (<80 fL) and/or increased RDW (>15%) on patients' initial complete blood cell count and moderatesevere HAA using multivariable modified Poisson regression. Moderatesevere HAA was more common in patients with high RDW and low MCV (45.5%), high RDW and MCV ≥80 fL (33.0%), and normal RDW and low MCV (28.0%) than in those with normal RDW and MCV (18.3%, p <0.001). Compared to patients with normal RDW and MCV, those with increased RDW and low MCV (relative risk 1.72, 95% confidence interval 1.57 to 1.87), increased RDW and MCV ≥80 fL (relative risk 1.28, 95% confidence interval 1.16 to 1.42), or normal RDW and low MCV (relative risk 1.34, 95% confidence interval 1.08 to 1.65) were independently more likely to develop moderatesevere HAA. In conclusion, increased RDW and low MCV were independent predictors of moderatesevere HAA.