We analyzed the frequency of cardiac embolic sources in 62 patients with acute lacunar stroke vs 50 controls. In post hoc analysis, 11 patients with lacunar stroke having neither hypertension nor diabetes mellitus (non-HDM group) had a higher frequency of right-to-left shunt (RLS) (82%) than patients with risk factors for lacunar stroke. RLS was also independently associated with the non-HDM group. Thus, RLS may contribute to lacunar stroke in patients without risk factors for lacunar stroke.