Introduction & Objective: Epidermolysis bullosa is a genetic disease, belonging to mechanobullosa family, It has 3 types: simplex, junctional, and dystrophic, It is characterised by easy detachment of epidermis from dermis, and mouth, teeth, esophagus, perineal area and other organs are involved, hand involvement is very severe, and it leads to mitten hand. The treatments performed in these patients consist of using skin graft of the patient himself, apligraft, keratinocyte, amnotic membrane, etc. Considering the brilliant effects of omniotic membrane and fibroblast in wound healing, both of them are used for hand coverage after the surgery.Materials & Methods: This study is a clinical trial on 10 patients with Epidermolysis bullosa with age within range of 5 to 30 years these patients were divided in 2 groups: one group using amniotic membranes only. The second group used amniotic membranes in combination with fibroblast. Skin samples from patient’s of posterior auricule, and fibroblasts were isolated, and were cultured and transferred to amniothic membrane. Then after operation and releasing the palm and finger and placing the krischner wire, to cover their hands, of amniotic membrane was used in the first group and amniotic membranes with fibroblasts were used in the second group. Then the two groups were followed and compared regarding the status of wound healing, graft take success, wound healing time, the number amniotic membranes, duration of hospitalization, number of surgeries and of total range of movement in at intervals of 1, 3 and 6 months.Results: Comparing the two groups, it become evident that the quality of wound healing, graft take rate, wound healing time were much better in fibroblastic group, and the duration of hospitalization and number of surgeries performed in the group using fibroblast and amniotic membranes was much smaller than group one which used amniotic membrane alone.Conclusions: There is various methods of treatment for EB including taking Graft from the patient, and using apligraft grafts, keratinocyte Biobrane, and amniotic membranes. Because of useful and interesting properties of amniotic membranes and fibroblasts in wound healing, the combination of both was used for the treatment of EB and significant benefits and effects were found in wound healing.