BACKGROUND. An increase in frequency of acute ischemic strokes has been observed among patients presenting with acute neurologic symptoms during the coronavirus disease (COVID-19) pandemic. OBJECTIVE. The purpose of this study was to investigate the association between COVID-19 and stroke subtypes in patients presenting with acute neurologic symptoms. METHODS. This retrospective case-control study included patients for whom a code for stroke was activated from March 16 to April 30, 2020, at any of six New York City hospitals that are part of a single health system. Demographic data (age, sex, and race or ethnicity), COVID-19 status, stroke-related risk factors, and clinical and imaging findings pertaining to stroke were collected. Univariate and multivariate analyses were conducted to evaluate the association between COVID-19 and stroke subtypes. RESULTS. The study sample consisted of 329 patients for whom a code for stroke was activated (175 [53.2%] men, 154 [46.8%] women; mean age, 66.9 +/- 14.9 [SD] years). Among the 329 patients, 35.3% (116) had acute ischemic stroke confirmed with imaging; 21.6% (71) had large vessel occlusion (LVO) stroke; and 14.6% (48) had small vessel occlusion (SVO) stroke. Among LVO strokes, the most common location was middle cerebral artery segments M1 and M2 (62.0% [44/71]). Multifocal LVOs were present in 9.9% (7/71) of LVO strokes. COVID-19 was present in 38.3% (126/329) of the patients. The 61.7% (203/329) of patients without COVID-19 formed the negative control group. Among individual stroke-related risk factors, only Hispanic ethnicity was significantly associated with COVID-19 (38.1% of patients with COVID-19 vs 20.7% of patients without COVID-19; p = 0.001). LVO was present in 31.7% of patients with COVID-19 compared with 15.3% of patients without COVID-19 (p = 0.001). SVO was present in 15.9% of patients with COVID-19 and 13.8% of patients without COVID-19 (p = 0.632). In multivariate analysis controlled for race and ethnicity, presence of COVID-19 had a significant independent association with LVO stroke (odds ratio, 2.4) compared with absence of COVID-19 (p = 0.011). CONCLUSION. COVID-19 is associated with LVO strokes but not with SVO strokes. CLINICAL IMPACT. Patients with COVID-19 presenting with acute neurologic symptoms warrant a lower threshold for suspicion of large vessel stroke, and prompt workup for large vessel stroke is recommended.