BACKGROUND: In divers, the significance of a patent foramen ovale and its potential relation to paradoxical gas emboli remain uncertain. OBJECTIVE: To assess the prevalence of symptoms of decompression illness and ischemic brain lesions in divers with regard to the presence of a patent foramen ovale. DESIGN: Retrospective cohort study. SETTING: University hospital and three diving clubs in Switzerland. PARTICIPANTS: 52 sport divers and 52 nondiving controls. MEASUREMENTS: Prevalence of self-reported decompression events, patent foramen ovale on contrast transesophageal echocardiography, and ischemic brain lesions on magnetic resonance imaging. RESULTS: The risk for decompression illness events was 4.5-fold greater in divers with patent foramen ovale than in divers without patent foramen ovale (risk ratio, 4.5 [95% CI, 1.2 to 18.0]; P = 0.03). Among divers, 1.23 +/- 2.0 and 0.64 +/- 1.22 ischemic brain lesions per person (mean +/- SD) were detected in those with and those without patent foramen ovale, respectively. Among controls, 0.22 +/- 0.44 and 0.12 +/- 0.63 lesion per person were detected (P < 0.001 for all groups). CONCLUSIONS: Regardless of whether a diver has a patent foramen ovale, diving is associated with ischemic brain lesions.