Hereditary hemochromatosis is a common genetic disorder characterized by progressive iron overload that may lead to multi organ damage if untreated. The aim of this review was to compare the efficacy, safety, and treatment characteristics of erythro cytapheresis and phlebotomy in adults with HFE-related hereditary hemochromatosis. A literature search was conducted using PubMed and Google Scholar to identify studies published after 2012 that directly compared both treatment modalities in adult patients. Available evidence indicated that both phlebotomy and erythrocytapheresis were effective in reducing iron overload and achieved comparable long-term control of serum ferritin and transferrin saturation. Erythrocytapheresis allowed removal of a greater amount of iron per procedure and was associated with fewer treatment sessions and a shorter induction phase. Adverse events were predominantly mild and transient. Although the cost per procedure was higher for erythrocytapheresis, overall treat ment costs appeared comparable when reduced procedure frequency and indirect costs were considered. Phlebotomy remains the first-line therapy for most patients; however, erythrocytapheresis represented a safe and effective alternative in selected individuals, particularly when rapid iron depletion or improved treatment tolerability was required.