OBJECTIVE: The aim of this study was to evaluate patient compliance with phlebotomy therapy of hemochromatosis-associated iron overload. METHODS: We reviewed medical records of white adults with hemochromatosis and iron overload diagnosed during medical care. We defined three elements of compliance: 1) achieving iron depletion (serum ferritin ≤ 20 ng/ml); 2) timeliness of phlebotomies on a weekly or biweekly schedule to achieve iron depletion; and 3) participation in therapy to maintain serum ferritin ≤ 50 ng/ml. We evaluated associations of timeliness of phlebotomy and participation in maintenance therapy with these variables: age at diagnosis, sex, pretreatment serum ferritin concentration, HFE genotype, units of blood removed to achieve iron depletion, and presence or absence of cirrhosis at diagnosis. RESULTS: A total of 118 patients were evaluable for iron depletion and 142 for maintenance therapy; 96.6% achieved iron depletion, and 33.1% and 43.2% followed weekly and biweekly schedules, respectively. Timeliness was not significantly associated with the variables we evaluated. In the first year of maintenance therapy, 84. 0% of patients complied; the percentage of C282Y homozygotes complying was significantly greater than that of other patients. Average compliance with maintenance therapy decreased 6.8% annually; the mean follow-up after achieving iron depletion was 4.1 ± 2.8 yr (range 0.6-9.7 yr). CONCLUSIONS: Most patients with hemochromatosis diagnosed in medical care achieve iron depletion with phlebotomy; one-third tolerate and adhere to weekly phlebotomy. There is a constant rate of decline in the percentage of patients who comply with maintenance therapy. © 2003 by Am. Coll. of Gastroenterology.