Background Systemic sclerosis is an autoimmune disease characterized by multisystem affection that could involve the gastrointestinal tract in the form of gastric antral vascular ectasia (GAVE) that might cause iron-deficiency anemia. Objective Evaluation of the outcome and the experience of management of iron deficiency anemia resulting from GAVE in patients with scleroderma using cyclophosphamide therapy compared with argon plasma coagulation (APC). Patients and methods This study was conducted over a 2-year period from February 2015 to February 2017. Scleroderma patients with GAVE and iron deficiency anemia were treated with cyclophosphamide (group I) others with APC application to areas with mucosal vascular lesions (group II). Results In total, 14 scleroderma patients with iron deficiency anemia resulting from associated GAVE were enrolled into two groups: group I included seven patients who were treated with cyclophosphamide infusion and group II were exposed to APC in sessions. Patients were followed up at 3 and 6 months; the endpoint was a complete response with improved anemia [hemoglobin (HB) and blood indices], and it was achieved in both groups as we found in group I patients there was a highly significant improvement (P<0.001) in HB, 3 and 6 months after therapy and in group II patients there was a highly significant improvement (P<0.001) in iron level 3 and 6 months, HB 6 months after. On comparing both groups it was clear that there was a significant improvement in group I as regards HB and ferritin levels 3 and 6 months after treatment when compared with group II, and highly significant increase in serum iron level 6 months after treatment in group I when compared with group II. Conclusion We found that cyclophosphamide and APC are highly efficacious and safe in controlling anemia resulting from scleroderma-associated GAVE. Also, cyclophosphamide is more efficient than APC in improving in those patients.