Background: An altered balance of gonadal hormones in males with gender identity disorders (GIDs) may increase multiple sclerosis (MS) risk both inherently and secondary to treatment in undergoing male-to-female conversion. Objective: We investigated any association between GIDs and MS through analysis of record-linked hospital statistics. Method: Analysis of English Hospital Episode Statistics, 1999-2012. Results: The adjusted rate ratio (RR) of MS following GIDs in males was 6.63 (95% confidence interval (95% CI) = 1.81-17.01, p = 0.0002). The RR of MS following GIDs in females was 1.44 (95% CI = 0.47-3.37, p = 0.58). Conclusion: We report a strong association between GIDs and MS in male-to-females, supporting a potential role for low testosterone and/or feminising hormones on MS risk in males.