BACKGROUND Although sex differences have been emphasized in stroke and congenital heart disease, there has been limited investigation on their role in patent foramen ovale (PFO). In fact, key guidelines on the management of PFO do not comment on sex or gender specific considerations in characteristics or outcomes of patients. We aimed to explore differences by sex in baseline profiles, procedural characteristics, and short-term outcomes of patients undergoing transcatheter PFO closure. METHODS AND RESULTS Data of adult patients undergoing transcatheter PFO closure at the Toronto General Hospital from 1997 to 2017 was retrospectively analyzed. Baseline information included demographic characteristics, medical history, diagnostic and procedural information, and periprocedural complications. Post-closure outcomes were captured at index hospitalization and during the first follow-up visit. From 1,032 patients in the cohort sample, 80.7% underwent closure for cryptogenic stroke and 44.8% (n=462) were females. We observed significant sex-related differences at baseline; females were younger, less likely to have a history of smoking, and less likely to have cardiovascular risk factors such as dyslipidemia and coronary artery disease (p < 0.05). No differences were observed in procedural and in-hospital outcomes between sexes. At the first follow-up, recurrent cerebrovascular events were reported in 1.5% and 1.9% of patients in the ‘cryptogenic stroke/TIA indications’ and ‘other indications’ groups respectively, with no significant differences by sex. There were significant sex differences between some symptom presentation both pre- and post-closure, with females more likely to present with migraine symptoms at both timepoints (p < 0.05). CONCLUSION Although no differences in procedural and short-term outcomes between males and females undergoing transcatheter PFO closure were observed, significant baseline differences in characteristics may justify the need for sex-specific risk assessment and PFO closure criteria. There is a critical need for long-term, systematic studies to understand sex and gender differences in the PFO population. Although sex differences have been emphasized in stroke and congenital heart disease, there has been limited investigation on their role in patent foramen ovale (PFO). In fact, key guidelines on the management of PFO do not comment on sex or gender specific considerations in characteristics or outcomes of patients. We aimed to explore differences by sex in baseline profiles, procedural characteristics, and short-term outcomes of patients undergoing transcatheter PFO closure. Data of adult patients undergoing transcatheter PFO closure at the Toronto General Hospital from 1997 to 2017 was retrospectively analyzed. Baseline information included demographic characteristics, medical history, diagnostic and procedural information, and periprocedural complications. Post-closure outcomes were captured at index hospitalization and during the first follow-up visit. From 1,032 patients in the cohort sample, 80.7% underwent closure for cryptogenic stroke and 44.8% (n=462) were females. We observed significant sex-related differences at baseline; females were younger, less likely to have a history of smoking, and less likely to have cardiovascular risk factors such as dyslipidemia and coronary artery disease (p < 0.05). No differences were observed in procedural and in-hospital outcomes between sexes. At the first follow-up, recurrent cerebrovascular events were reported in 1.5% and 1.9% of patients in the ‘cryptogenic stroke/TIA indications’ and ‘other indications’ groups respectively, with no significant differences by sex. There were significant sex differences between some symptom presentation both pre- and post-closure, with females more likely to present with migraine symptoms at both timepoints (p < 0.05). Although no differences in procedural and short-term outcomes between males and females undergoing transcatheter PFO closure were observed, significant baseline differences in characteristics may justify the need for sex-specific risk assessment and PFO closure criteria. There is a critical need for long-term, systematic studies to understand sex and gender differences in the PFO population.