Background: Vitiligo is a common skin disorder characterized by depigmentation. A number of hypotheses exist to explain the aetiology. Recently evidence suggested that polymorphisms of some genes are associated with vitiligo risk. Here, we want to study the possible association between the inducible nitric oxide synthase (iNOS) gene polymorphism and the risk of vitiligo in a sample group of the Egyptian patients. Patient and methods: The current study included 100 vitiligo patients and 100 healthy controls who where subjected to genotyping of iNOS gene polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results were correlated with the patient's sex, age, type of vitiligo, association of autoimmune disease, duration &extent of the disease. Results: In the current study 100 patients with vitiligo and 100 age- and sex matched healthy controls, two polymorphisms of iNOS gene were genotyped by using the (PCR-RFLP) technique. We found the iNOS-954 polymorphism was associated with a significantly higher risk of vitiligo in Egyptian population (OR= 3.35, 95%CI= 1.77- 6.33). Regarding the iNOS Ex 16+14 polymorphism was also associated with a significantly higher risk of vitiligo in Egyptian population (OR= 2.47, 95% CI= 1.39 – 4.37). Conclusion: This study suggests an important link between the inducible nitric oxide synthase gene polymorphism and occurrence of vitiligo especially in females.