BACKGROUND: Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke. METHODS AND RESULTS: We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy, defined as left ventricular ejection fraction ≤45%. Among 938 consecutive patients, 46 (4.9%) were identified as using methamphetamine. Compared with the nonmethamphetamine group (n=892), the methamphetamine group was significantly younger (52.8±9.6 versus 69.7±15.2 years; P<0.001), included more men (78.3% versus 52.8%; P<0.001), and had a significantly higher rate of cardiomyopathy (30.4% versus 14.0%; P<0.01). They were also less likely to have a history of atrial fibrillation (8.7% versus 33.4%; P<0.01) or hyperlipidemia (28.3% versus 51.7%; P<0.01). Compared with patients with cardiomyopathy without methamphetamine use, the patients with cardiomyopathy with methamphetamine use had significantly lower left ventricular ejection fraction (26.0±9.59% versus 32.47±9.52%; P<0.01) but better functional outcome at 3 months, likely attributable to significantly younger age and fewer comorbidities. In the logistic regression model of clinical variables, methamphetamine-associated cardiomyopathy was found to be significantly associated with cardioembolic stroke (odds ratio, 1.79 [95% CI, 1.04-3.06]; P<0.05). CONCLUSIONS: We demonstrate that methamphetamine use is significantly associated with cardiomyopathy and cardioembolic stroke in young adults.