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Highlights •This study combined ALDH activity with cell surface marker expression to develop a multiparametric flow cytometry assay to assess proangiogenic progenitor and proinflammatory cell content in the peripheral blood of patients with T2D compared with age-matched control subjects. •Patients with T2D exhibited an increased frequency of proinflammatory ALDHhi cells with granulocyte side scatter properties and a decreased frequency of circulating monocytes with an M2 phenotype that is associated with proangiogenic and anti-inflammatory functions. •Patients with T2D exhibited significant depletion of circulating provascular ALDHhiCD34+ progenitor cells with primitive, migratory, endothelial, and pericyte phenotypes. •Subgroup analyses that stratified patients with T2D according to age, duration of T2D, insulin requirement, and glycosylated hemoglobin levels revealed that only the duration of T2D correlated with vascular progenitor cell depletion. •Flow cytometric assessment of circulating ALDHhi cell subsets represents a promising translational approach for identifying patients with T2D at increased risk for cardiovascular comorbidities.