AIM: To explore the causal association between the counts of five types of white blood cells—neutrophils, monocytes, eosinophils, basophils, and lymphocytes—and venous thromboembolism (VTE). METHODS: Mendelian randomization (MR) analysis method was used, with genetic variants associated with the five types of white blood cells as instrumental variables, and venous thromboembolism occurrence risk as the outcome variable, inverse variance-weighted (IVW) method was employed as the primary analysis method, with MR-Egger regression, weighted median (WM), simple model, and weighted mode methods used as supplements, to analyze the causal association between the counts of five types of white blood cells and VTE, followed by reverse MR analysis. RESULTS: Neutrophil and lymphocyte counts are causally associated with the risk of VTE. For neutrophil count, the IVW estimate (OR=0.867, 95%CI: 0.761-0.981, P=0.031), MR-Egger estimate (OR=0.754, 95%CI: 0.571-0.996, P=0.048), weighted median estimate (OR=0.846, 95%CI: 0.729-0.981, P=0.027), and weighted model estimate (OR=0.748, 95%CI: 0.595-0.942, P=0.014) were calculated. For lymphocyte count, the IVW estimate (OR=0.838, 95%CI: 0.741-0.949, P=0.005) and weighted median estimate (OR=0.024, 95%CI: 0.718-0.977, P=0.024) were calculated. Reverse MR analysis showed a causal association between the risk of VTE and neutrophil count, the IVW estimate (OR=0.989, 95%CI: 0.980-0.999, P=0.024). CONCLUSION: Neutrophil and lymphocyte counts are related to the risk of VTE, and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE. VTE occurrence risk is associated with neutrophil count, and reducing the risk of VTE occurrence may increase neutrophil count. Further research is needed to understand the underlying biological mechanisms behind this relationship.