Hemophilia A (HA) is one of the most prevalent X-linked recessive inherited coagulation disorder of variable severity .It occurs in approximately one in every 5,000 male births worldwide ,and encompassing almost 80–85% of hemophilic patients. The disease is caused by deleterious mutations in the factor VIII gene (FVIII) resulting in a dysfunction of coagulation factor VIII an essential cofactor of the intrinsic pathway of the clotting mechanism. Haemophilia A is considered as a health problem in Oman. 156 patients have been diagnosed with severe haemophilia A. There have been no genetic studies done previously to determine the molecular Vere defects causing this disease. The current study aims to identify FVIII gene mutations in HA patients in Oman. Twelve HA were included in this study. Genomic DNA was isolated from blood by DNA Midi Kit QIAGEN. To screen the genomic DNA for molecular defects, the following was done. First, Screening for inv-1 and inv-22 were done by IS-PCR method. Second, DNA sequencing was performed by Sanger method for all 26 exons of factor VIII gene. PCR products were sequenced using ABI 3130 Genetic analyzer. The sequence results were analyzed using SeqScape v2.6 and Bioedit programs. In order to predict the possible impact of a variation on the function of factor VIII gene, the online tools Polyphen 2, and Swiss-pdb Viewer were used. Out of 12 patients tested, 1 patient was positive for inv-1 and 8 patients were positive for inv-22 (68%). 2 novel missense mutations were found, c.1594T>C, p. (W532R) in exon 11 in one of the patient which was associated with severe hemophilia A phenotype and c.446C>G, p. (P149A) in exon 4 in another patient which was associated with mild hemophilia A phenotype. We conclude that inv-22 is responsible for about two third of disease causing mutations in sever haemophilia A patients in our samples. The data presented in this study can be used for genetic counselling. It also can be used as the basis of future genetic analysis of the disease