Anemia is frequent in older adults. The essential mechanisms underlying its pathogenesis and relationship with clinical outcomes have been investigated. Erythroid-stimulating agents, particularly recombinant erythropoietin (EPO), corrected anemia in older adults and improved their clinical outcomes. Notwithstanding, many questions remain unanswered. The aim of this study was to correlate a few components of the comprehensive geriatric assessment, such as frailty index, time to up and go test, and mini mental state examination with hemoglobin levels (Hb) after treatment with EPO and blood transfusion, and to determine improvements in outcomes after treatment. 256 patients with anemia aged 65 or older were evaluated, but only 101 hospitalized cases completed the follow-up. They were allocated to three groups: group 1 received recombinant EPO 40,000 U/week, group 2 EPO 4000 U three times a week, and group 3 transfusions as needed. No statistically significant difference was observed between group 1 and group 2. All patients underwent a geriatric evaluation based on the time up and go test (TUGT), the mini mental test, the frailty index, and the occurrence of events such as delirium and falls. EPO resulted in erythroid response in nearly 70% of the treated cases and increased Hb (p < 0.001). There was no correlation between anemia and mortality or adverse events, except for such cardiovascular events as heart failure, angina, and syncope. There was a correlation of Hb levels with less frailty and falls (p < 0.001). EPO treatment was also associated with functional improvement, as indicated by TUGT. These findings indirectly support the view that anemia is an independent risk factor for executive function impairment in hospitalized older adults.