Patent foramen ovale (PFO) appears to be associated with migraine with aura (MA), probably through cardiac shunting. PFOs may also be comorbid with cryptogenic strokes. Although multiple open-label, retrospective, and case-controlled studies have noted sometimes dramatic reductions of MA after PFO closure, the only prospective sham-controlled study of PFO closure for MA, MIST, was negative for all primary and secondary measures of migraine improvement. MIST did demonstrate an association between MA and severe PFO shunts prospectively. Difficulty with recruitment closed the MIST II and ESCAPE trials; the PREMIUM and PRIMA randomized controlled trials are ongoing at the time of this writing.