Objective: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.Methods: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.Results: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. Conclusion:Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk. Case-control studies suggest that patent foramen ovale (PFO) is a common cause of cryptogenic stroke (CS), likely through a paradoxical (venous-to-arterial) embolism.1,2 However, CS has many potential causes, and PFO is a common anatomical variant found in approximately 25% of the general population.3 Thus, a PFO discovered in the setting of a CS may be incidental or stroke-related.Percutaneous mechanical closure of a PFO is frequently considered in patients with CS and PFO. The recently reported CLOSURE trial, however, found no benefit for this approach over medical therapy. 4 Nonetheless, stroke recurrence rates were low overall (limiting statistical power) and most stroke recurrence in both treatment groups was due to stroke of known mechanism, suggesting that many patients with incidental PFOs may have been enrolled.The premise of the Risk of Paradoxical Embolism (RoPE) Study 3 is that only patients with a high attributable recurrence risk have the opportunity to benefit from PFO closure for secondary