The administration of intravenous (IV) iron to treat anemia during acute infection remains controversial due to concerns of exacerbating the infection. We conducted a retrospective cohort study using the TriNetX Research Network (2000 to June 2025) to evaluate the safety and efficacy of IV iron administration in adults with iron-deficiency anemia and infection (methicillin-resistant Staphylococcus aureus [MRSA] bacteremia, pneumonia, urinary tract infection [UTI], colitis, or cellulitis). Patients must have received antibiotics within 2 days of infection for inclusion and were stratified by IV iron exposure. Propensity matching (1:1) was performed within each cohort. Survival was significantly higher (p<0.001 for each infection type) at both 14 and 90 days in patients who received IV iron (MRSA bacteremia 97.6% vs 95.0% and 88.6% vs 83.8%; pneumonia 95.7% vs 91.5% and 84.7% vs 78.1%; UTI 97.6% vs 95.7% and 89.1% vs 85.6%; colitis 97.6% vs 95.5% and 89.7% vs 83.8%; and cellulitis 98.5% vs 97.4% and 92.2% vs 89.2%). Hemoglobin recovery 60-90 days after infection was significantly greater (all p<0.001) when IV iron was administered across all subgroups (MRSA bacteremia +1.3 vs +1.0 g/dL; pneumonia +1.3 vs +1.0 g/dL; UTI (+1.4 vs +1.0 g/dL; colitis +1.5 vs +0.7 g/dL; and cellulitis +1.4 vs +0.9 g/dL). The findings observed for each infection type studied suggest that IV iron administration during acute infection does not exacerbate infection and is associated with improved survival and enhanced recovery from anemia in hospitalized patients. Prospective studies are needed to confirm these findings and expand their applicability.