Background--Metformin use reduces the incidence and severity of stroke in patients with type 2 diabetes mellitus (DM). The benefits of metformin for stroke have not been examined in hemodialysis patients with DM. Methods and Results--Using the National Health Insurance Research Database, we identified 17 760 patients with DM and newonset hemodialysis between 2001 and 2013. Of these, 1898 patients hospitalized for either ischemic or hemorrhagic stroke were matched to 7592 control patients according to sex, age, and year of initial hemodialysis therapy by using incidence sampling. The association between metformin use and stroke risk was estimated using conditional logistic regression after adjustment for hemodialysis frequency, comorbidity, and prescribed medications. Metformin use was recorded before the date of stroke admission and the date of pseudostroke of the case and control patients, respectively. Results showed that hemodialysis patients with ischemic stroke were more likely to use metformin than the controls 1 year before the date of stroke admission (adjusted odds ratio: 1.64; 95% confidence interval, 1.32-2.04). The association was evident within 90 days before the index date (adjusted odds ratio: 1.81; 95% confidence interval, 1.27-2.60). The results were consistent with those of hemodialysis patients with hemorrhagic stroke. Metformin use remained a risk factor for stroke in patients treated with antihypertensive, sulfonylurea, and antiplatelet drugs. Conclusions--This nested case-control study is the first to show that metformin use is associated with stroke risk in hemodialysis patients with DM. We suggest that metformin should not be used by hemodialysis patients with DM.