The present study assessed the frequency of intron 22 inversion mutation (Inv 22) in north Indian population with a cost analysis of different methods used for Inv 22 detection. We assessed the frequency of intron 22 inversion mutation in a series of 181 cases with hemophilia A and also compared methods used for detection of the mutation including the long-distance PCR, Southern blot analysis, and inverse PCR in terms of cost, infrastructure, and technical input as well as turnaround time. The study group comprised 102 severe cases and 79 moderate cases of hemophilia A from a north Indian population of which 77 cases tested positive for Inv 22. The observed frequency of Inv22 mutation was 42.5%. Inv 22 resulted in a more severe phenotype and lower FVIII bioassay levels as compared to Inv 22 negative cases. Inv 22 positive cases also frequently presented with bleeding episodes at birth and the mean age for commencement of bleeding was lower (19 months) as compared to Inv-negative cases (50 months). The mean frequency of Inv 22 in cases with hemophilia A in a worldwide review is 44.25% of hemophilia A. Inv 22 can be conveniently detected by using the inverse PCR method. This technique is easy to standardize and lowest in cost.