Objective: The clinical and echocardiographic parameters associated with the risk predictors of cryptogenic stroke (CS) in patients with patent foramen ovale (PFO) still diverse and with a great debate. We hypothesized that left atrial stiffness (LASt) and atrial dyssynchrony may increase the risk of CS in patients with PFO. Methods: A total of 129 consecutive patients presented without clinical reasoning of stroke were recruited. Transesophageal echocardiographic assessment was performed to investigate the presence of PFO. PFO was identified in 52% (group I) and absent in 48% (group II). Utilizing speckle-tracking imaging LASt and atrial dyssynchrony was evaluated among patients with PFO (group I) vs those without PFO (group II). Results: LASt was significantly increased in group I patients compared with group II (P < .001). Likewise patients with PFO had a significant LA dyssynchrony compared with those in group II (P < .001). Interatrial dyssynchrony and left atrial dyssynchrony were correlated with LASt (r = .47 and 0.51, respectively; P < .001). Cardiac arrhythmias were significantly encountered in group I patients (at presentation and with Holter monitoring) P < .001. Besides significantly increase in atrial dyssynchrony and in LASt in patients with arrhythmias compared with those without (P < .001). ROC analysis revealed that LASt index ≥ 0.61 and LA dyssynchrony ≥ 23.5 predicts cardiac arrhythmias in CS patients with PFO with (AUC: 0.85 and 0.87, respectively, P < .001). Conclusion: In conclusion, we demonstrated that LASt and atrial dyssynchrony might be risk markers of cryptogenic stroke in patients with PFO.