Purpose: The association between the presence of patent foramen ovale (PFO) and cryptogenic stroke in older patients is controversial. Intrapulmonary shunt is frequently detected in agitated saline contrast echocardiography but its clinical significance was not established. We aimed to determine the association between patent foramen ovale, intrapulmonary shunt (IPS), cryptogenic stroke in older patients. Methods: We examined 557 consecutive patients at the age of 55 years or older who had a stroke. The cause of ischemic infarction was classified according to TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. We compared the 118 patients with cryptogenic stroke and the 439 patients with known causes. We identified PFO, using transthoracic echocardiography with harmonic imaging and agitated saline contrast. If bubbles appear in the left atrium within 3 cardiac cycles from maximal opacification of right atrium, PFO is diagnosed, whereas IPS is diagnosed, if bubbles appear after 3 cardiac cycles from pulmonary vein. Results: The prevalence of PFO showed no significant difference between patients with cryptogenic stroke and those with known causes (17% vs. 12.6%, p=0.15). IPS was more frequently observed than PFO (15% vs. 12.7%) and its prevalence was significantly greater among patients with cryptogenic stroke than among those with stroke of known cause (21% vs. 13.3%, p=0.03). Mutivariate analysis adjusted for age, mitral annular calcification, aortic valve sclerosis and hypertension revealed that the presence of PFO or IPS was independently associated with cryptogenic stroke (odds ratio, 1.8; 95% CI, 1.09 to 3.02; p=0.021). Conclusions: Our data showed that IPS with PFO has a strong association with cryptogenic stroke in older patients but not PFO alone. A prospective cohort study is required to confirm the potential role of IPS in cryptogenic stroke.