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BackgroundPrevious studies have shown that various cell indices are associated with a higher risk of venous thromboembolism (VTE), however, whether these findings reflect a causal relationship remains unclear. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to assess the causal association of various blood cells with VTE risk.Study Design and MethodsSummary statistics of genetic instruments representing cell indices for erythrocytes, leukocytes, and platelets were extracted from genome-wide association studies of European ancestry, by Two-Sample Mendelian Randomization. Inverse variance weighting (IVW) was used as the primary analytical method for MR. Sensitivity analyses were performed to detect horizontal pleiotropy and heterogeneity.ResultsGenetically predicted red blood cell distribution width, mean reticulocyte volume, and mean red blood cell volume were positively associated with VTE, with odds ratio (OR) of 1.002 [CI 1.000–1.003, P = 0.022), 1.003 (CI 1.001–1.004, P = 0.001, respectively)] and 1.001 (CI 1.000–1.002, P = 0.005). Genetically predicted monocyte count was negatively correlated with VTE, with OR = 0.998 (CI 0.996–0.999, P = 0.041).ConclusionGenetically liability to high- red blood cell distribution width, mean reticulocyte volume, mean red blood cell volume, and low monocyte count are associated with the higher risk of VTE. Targeting these factors might be a potential strategy to prevent VTE.