Background: Numerous studies in adults have reported a robust association between patent foramen ovale (PFO) and cryptogenic arterial ischemic stroke (AIS), particularly in younger adults. The association between PFO and stroke in children has not been well characterized and the clinical significance of identifying a PFO in a child with first or recurrent cryptogenic stroke is currently unknown. Methods: We performed a retrospective case control analysis of a 10-year prospectively enrolled cohort of children with acute AIS who underwent transthoracic echocardiogram (TTE) as part of their diagnostic evaluation. We compared PFO prevalence in children with cryptogenic stroke to those with known stroke etiologies and to non-stroke controls. We also assessed stroke recurrence risk in children with vs without PFO and assessed PFO features that may confer higher stroke risk. Results: Of 119 children with first-ever AIS, 59 had TTE available for central review, of which 17 were cryptogenic and 42 had a known cause. PFO prevalence was higher in the cryptogenic stroke group (X, 24%) compared to both the known stroke etiology group (Y, 6%, p = 0.05) and non-stroke controls (Z, 8%, p = 0.05). However, 2 year recurrence free survival rates in stroke patients with PFO did not differ from those without PFO (HR 1.58, 95% CI 0.18-13.62, p = 0.68). PFOs in children with AIS vs controls had numerically more right-to-left shunt at rest (7 vs 0) and atrial septal aneurysm (4 vs 0) but the study was underpowered to look at these factors. Conclusions: In our prospectively enrolled cohort of children with AIS, we found the prevalence of PFO to be higher in children with cryptogenic stroke compared to healthy controls and non-cryptogenic stroke patients. The implication of PFO for risk of recurrence and optimal secondary preventative treatment remains uncertain and require further study.