Behcet’s disease is a systemic disorder where its etiopathogenesis is not well determined and commonest manifestations are muccocutaneous but can involve eye, cardiovascular and neurological systems. There are many modalities of therapy topical and systemic. Isotretinoin has been tried as an effective therapy of muccocutaneous manifestations. In present work is to try a new retinoid like acitretin which has longer half life than isotretinoin. To evaluate the effectiveness of oral acitretin versus oral zinc gluconate in the treatment and prophylaxis of BD as a new therapeutic model. This cross over controlled therapeutic study that conducted in the Department of Dermatology -Baghdad Teaching Hospital the period from August 2013-May 2014.Twenty patients who fulfilled criteria of BD are included in this work and the investigation were included ordinary and oral pathergy test. They were given acitretin 25 mg orally once daily for three months to be seen on the day fourteenth firstly and then monthly to be assessed depending on the clinical manifestation index for Behcets disease. After three months, acitretin was stopped and patients were given 25 mg elemental zinc gluconate twice daily for another three months. Twenty patients were treated, 12 males (60%), and 8 females (40%), with male to female ratio 1.5:1. All these patients completed the study and their ages ranged between 20-59 (37.3±12.3) years. Pathergy both ordinary and oral were also minimized by this therapy while C- reactive protein was not much effective by this therapy. Zinc gluconate had also the same therapeutic action against these manifestations. CMI before treatment ranged between 1 and 11 (5.65±1.98). After acitretin therapy the mean of CMI started to decline to reach 2.65 ±2.03 in first month of the therapy, with (p=0.00001) which was statistically high significant and continued high significant till the end of the third month. After cessation of acitretin and zinc gluconate started the mean continued to decrease to reach 2.05±2.52 at the end of the first month which was statistically high significant then; started to increase to reach 3.3 ±2.31 at the end of six month of the therapy but statistically remained highly significant. Both acitretin and zinc gluconate had statistically significant effect in reducing severity and frequency of oral ulcers, genital ulcers, skin and rheumatologic manifestations. Acitretin and oral zinc gluconte had an effective therapy in addition to its prophylactic action in treatment of muccocutaneous manifestations of Behcet,s disease. Also acitretin was statistically significant better than zinc gluconate.