Objective To test the effect of patent foramen ovale (PFO) closure on neurological events in divers. Design Prospective, non-randomised, longitudinal three-arm study. Setting Tertiary referral centre. Population 104 scuba divers with a history of major decompression illness (DCI). Intervention Transcutaneous PFO closure. Main outcome measures Baseline and three follow-up examinations with a questionnaire about health status and diving habits/accidents, transoesophageal echocardiography at baseline for PFO grading, cerebral MRI at all examinations. Results 39 divers had no PFO, 26 had a PFO and chose to undergo percutaneous closure and 39 had a PFO, but decided not to undergo closure. The total number of dives, including those performed before baseline and those during long-term follow-up, was 81 654; 18 394 dives during the follow-up period of 5.3 +/- 0.3 years, during which there were a total of five major neurological DCI events-namely 0 in the no PFO group, 0.5 +/- 2.5/10(4) dives in the PFO closure group and 35.8 +/- 102.5/10(4) dives in the PFO no closure group (four events; p=0.045 between the PFO groups). In the groups, no PFO, PFO closure and PFO no closure, there were 1.1 +/- 2.6, 0.8 +/- 1.4, 3.3 +/- 6.9 ischaemic brain lesions, respectively, at follow-up (p=0.039 between the PFO groups)-that is, 16 +/- 42/10(4) dives in the no PFO group, 6 +/- 13/10(4) dives in the PFO closure group and 104 +/- 246/10(4) dives in the PFO no closure group (overall p=0.042; p=0.024 between the PFO groups). Conclusion PFO closure in continuing divers appears to prevent symptomatic (major DCI) and asymptomatic (ischaemic brain lesions) neurological events during long-term follow-up.