Development of hospital-acquired anemia (HAA) during acute myocardial infarction may be related to processes of care and is associated with poor outcomes. Little is known about variation in the incidence of HAA across hospitals or the hospital characteristics associated with HAA. We studied 17,676 patients with acute myocardial infarction without anemia at admission, defining HAA as a hemoglobin decline below anemia diagnostic thresholds and moderate-to-severe HAA as a hemoglobin decline to <11 g/dl. We calculated median rate ratios (MRRs), the median value of the relative risk (RR) for HAA for 2 patients with identical characteristics presenting to 2 randomly selected hospitals, to identify variation in HAA adjusting for patient characteristics. Separate models were fit to test the association between hospital characteristics and HAA. HAA (57.5%) and moderate-to-severe HAA (20.1%) were common. The incidence of HAA varied substantially across hospitals and remained significant after multivariable adjustment (any HAA: MRR 1.09, 95% confidence interval (CI) 1.07 to 1.13; moderate-to-severe HAA: MRR 1.27, 95% CI 1.19 to 1.39). Adjusting for patient characteristics, teaching status (RR 0.91, 95% CI 0.84 to 0.97 vs nonteaching status), and region (Northeast vs Midwest: RR 1.10, 95% CI 1.01 to 1.19; West vs Midwest: RR 1.19, 95% CI 1.06 to 1.33, respectively) was associated with risk of HAA. Teaching status (RR 0.7, 95% CI 0.6 to 0.9 vs nonteaching status) and region (South vs Midwest: RR 1.3, 95% CI 1.0 to 1.5) were independently associated with moderate-to-severe HAA. In conclusion, we observed significant variability in the incidence of HAA across hospitals and found a lower risk of HAA at teaching centers, suggesting that qualitative studies of the relation between HAA and processes of care are needed to identify targets for quality improvement.