Cryptogenic stroke is an ischemic stroke for which no etiology (such as large or small vessel atherosclerosis or cardioembolism) is identified following a complete diagnostic evaluation. It is therefore a diagnosis of exclusion. If the etiology is found, the stroke will not be considered cryptogenic. Cryptogenic stroke ultimately includes mechanisms such as patent foramen ovale (PFO), hypercoagulable states, and aortic arch atherosclerotic plaque. Cryptogenic stroke also includes stroke for which multiple mechanisms of stroke may be possible. Venous thromboembolism may result in stroke due to paradoxical embolism from a venous thromboembolism travelling through a PFO or cardiac septal defect. Occult atrial arrhythmias (particularly atrial fibrillation), cardiac malformations, cardiomyopathy, and vasculopathies are also proposed possible mechanisms for cryptogenic stroke.

Studies show that 25%-40% of ischemic strokes are cryptogenic without clear association with sex or age. Some studies have shown that the likelihood of cryptogenic stroke is higher in patients younger than 50 years and in Black and Hispanic patients than in White patients.

Patients with cryptogenic stroke will present with acute onset of focal neurologic symptoms such as focal weakness, sensory loss, vision loss, or aphasia.