Ischemic stroke (IS) is a major cause of morbidity and mortality globally. Environmental exposure to metals may be linked to the risk of IS, but the association remains uncertain in Chinese populations. The present study aimed to examine the associations between the concentrations of 11 metals (aluminum, arsenic, cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, thallium, and zinc) in plasma and the risk of IS in a Chinese population. A total of 1277 pairs of newly diagnosed IS patients and controls matched on age (±3 years) and sex were recruited in our study. Plasma metal concentrations were measured using inductively coupled plasma mass spectrometry. Multivariable conditional logistic regression models were conducted to investigate the impacts of single and multiple metals, respectively. In the single-metal model, exposure to seven metals (aluminum, arsenic, cadmium, cobalt, iron, manganese and selenium) was individually associated with the risk of IS based on the trend test. Further stepwise regression analyses with the multiple-metal model revealed increasing trends in the risk of IS associated with aluminum, arsenic, and cadmium quartiles and decreasing trends with iron and selenium quartiles (p-trend < 0.01). Compared to the lowest quartiles, the odds ratios (95% confidence intervals) for the highest quartiles of these five metals were 4.23 (2.63, 6.79), 1.88 (1.25, 2.81), 5.02 (3.30, 7.63), 0.59 (0.40, 0.89), and 0.10 (0.06, 0.17), respectively. Our study suggested that higher plasma concentrations of aluminum, arsenic, and cadmium, and lower concentrations of iron and selenium may increase the risk of IS. Further prospective studies in larger populations are warranted to confirm our findings. •First study on the associations of multiple plasma metals with ischemic stroke risk in China•Plasma Al, As, and Cd were positively associated with ischemic stroke risk•Plasma Fe and Se were negatively associated with ischemic stroke risk