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Background: Asthma prognosis is thought to be influenced in some part by age of onset and female hormonal status but the mechanisms remain unclear. Aim: To explore differences in clinical presentation between men and women in a population of adult onset difficult asthmatics. Methods: 380 patients aged 17-85 years were recruited into the Wessex AsThma CoHort of difficult asthma (WATCH). Asthma history, questionnaires and biological measurements were taken at enrolment. Those with onset ≥19 were split by sex to explore differences in disease. Results: Age of asthma diagnosis was available in 335 of 380 patients with 48% reporting diagnosis at 19 years or older. Men with adult onset difficult asthma had significantly later age of diagnosis and higher FeNO than women. Their perception of disease severity was less and BMI significantly lower than females. Men had higher IgE, lower propensity to salicylate sensitivity and greater level of airway obstruction though this was not specific to age of onset. Additional sex differences in lung function reported within the total WATCH cohort were not seen in this subset of difficult asthmatics. Significance a= Conclusion: Several features of difficult adult onset asthma differ by sex, suggesting potential sex-specific disease influences. This supports the need for further sex-specific studies that might result in new sex-stratified asthma treatments.