To assess the impact of anemia and iron deficiency on health-related quality of life (HRQoL) in women treated for heavy menstrual bleeding (HMB). Secondary analysis of a randomized controlled trial. Five university hospitals in Finland. A total of 236 women referred for HMB. Women were randomized to treatment with hysterectomy or a levonorgestrel-releasing intrauterine system. We defined groups based on women's pretreatment hemoglobin [hemoglobin <120 g/L (anemic) vs. hemoglobin ≥120 g/L (nonanemic)] and serum ferritin (ferritin <15 μg/L vs. ≥15 μg/L) concentrations. HRQoL was compared between groups at baseline, 6 and 12 months after treatment. Hemoglobin and ferritin were followed for 5 years. HRQoL was measured by the RAND 36-item health survey (RAND-36), 5-Dimensional EuroQol and two questionnaires of mental wellbeing. At baseline, 63 women (27%) were anemic and 140 (60%) were severely iron deficient (ferritin <15 μg/L). Only 8% of the anemic women had taken iron supplementation. Twelve months after treatment hemoglobin had increased in both hemoglobin groups, but was still significantly lower (p < 0.001) in initially anemic women (128 g/L) compared with nonanemic women (136 g/L). Twelve months after treatment three domain scores of RAND-36 increased more (energy, p = 0.002; physical functioning, p = 0.04; social functioning, p = 0.05), and anxiety (p = 0.02) and depression scores (p = 0.002) decreased more in anemic compared with nonanemic women. Serum ferritin took 5 years to reach normal levels. Improved HRQoL after treatment of HMB is associated with correction of anemia. Clinicians should actively screen for anemia in women with HMB and emphasize early iron substitution as an integral part of treatment.