Statins may protect against adverse outcomes from Coronavirus disease 2019 (COVID‐19) through their pleiotropic effects. Endothelial dysfunction seems to be implicated in the pathophysiology of COVID‐19, and can be attenuated by statins. This study assessed the role of preadmission statin therapy and its interaction with endothelial function, measured using flow‐mediated dilation (FMD) at hospital admission, in predicting in‐hospital outcomes among patients with COVID‐19 having high‐to‐very high cardiovascular (CV) risk. We conducted a retrospective cohort study of hospitalized patients with COVID‐19 having high‐to‐very high CV risk, including a subgroup of patients who underwent FMD assessment. Among 342 patients, 119 (35%) were treated with statins at study baseline. Preadmission statin therapy was independently associated with a 75% risk reduction of intensive care unit admission/in‐hospital death (adjusted hazard ratio 0.252, 95% confidence interval 0.122−0.521, p < 0.001). In the subgroup of patients with an FMD assessment (245 patients, 40% statin‐treated), preadmission statin therapy was independently associated with higher FMD values (β = 0.159, p = 0.013). However, preadmission statin therapy × FMD interaction was not associated with in‐hospital outcomes (F = 0.002, pinteraction = 0.960). Preadmission statin therapy is associated with better in‐hospital outcomes among patients with COVID‐19 having high‐to‐very high CV risk, independent of the endothelium‐protective effects of these drugs.