AbstractBackgroundThe identification of blood donors at risk of developing low hemoglobin (Hb) and subsequent intervention is expected to reduce donation‐induced iron deficiency and low Hb among blood donors. This study explores the effects of ferritin‐guided iron supplementation for female first‐time donors implemented in four of five administrative regions in Denmark.Study Design and MethodsWe included 45,919 female first‐time donors in this study. Hb values were determined in donations of included donors during a 2‐year follow‐up period. For each region, an intervention group (after implementation) and a control group (before implementation) were defined. The primary outcome was Hb below the donation threshold (7.8 mmol/L ~ 12.5 g/dL) at the time of donation, in the control group, and the intervention group, using logistic regression. The secondary outcome was the number of donations per donor given during the follow‐up period.ResultsWe observed a statistically significant decrease in the risk of female first‐time donors experiencing a donation with low Hb after ferritin‐guided iron supplementation was introduced: Odds ratio, 0.82; 95% confidence interval (CI), 0.71–0.95. We found a statistically significant increase in the number of donations per donor during the follow‐up period after intervention; rate ratio: 1.05, 95% CI: 1.02–1.08.DiscussionFerritin‐guided iron supplementation led to a significant reduction in the occurrence of low hemoglobin (Hb) levels among Danish female first‐time blood donors. The intervention was additionally associated with an increase in the number of donations per donor.