The new clinical construct of embolic stroke of undetermined source (ESUS) suggests that many cryptogenic strokes are related to minor-risk covert embolic cardiac sources or to embolus from non-occlusive plaques in the aortic arch or in the cerebral arteries. The authors analyzed the prevalence of ESUS in a real-life condition in Italy and compared the recurrence rates in cryptogenic strokes, cardioembolic strokes, and ESUS. The authors retrospectively reassessed according to ESUS criteria 391 consecutive admissions in a stroke unit where extensive diagnostic search was routinely performed. Recurrences in each stroke type within a 3-year follow-up period (mean time: 25.44 months - standard deviation: 9.42) were also compared. The prevalence of ESUS in the aforementioned cohort was 10.5%. All ESUS patients received antiplatelet agents. Warfarin was prescribed in 56.9% of cardioembolic strokes. The recurrence rate in ESUS patients was 4.4% per year, slightly higher than in cardioembolic strokes (3.5%) and significantly higher than in cryptogenic non-ESUS (1.2%) (P<0.0001). This is the first description of a cohort of ESUS patients in an Italian stroke unit. Patients with ESUS have a significantly higher risk of recurrence than in those with non-ESUS cryptogenic strokes, and slightly higher than in those with cardioembolic strokes. Results support the hypothesis of a more extensive diagnostic evaluation in cryptogenic strokes and the feasibility of such approach.