Background Multiple myeloma is a malignancy that affects the blood, and phlebitis involves inflammation and thrombosis of blood vessels. In clinical cases, patients with multiple myeloma are often accompanied by phlebitis. There may be some potential relationship between the two, but the specific mechanism is not clear. Objective To evaluate the relationship between phlebitis and multiple myeloma, and investigate whether the level of angiopoietin-1 receptor plays a mediating role in this relationship.Methods Two-way two-sample Mendelian randomization (MR) was used to analyze the GWAS data of phlebitis and multiple myeloma in IEU Open GWAS database, the relationship between phlebitis and multiple myeloma were investigated, and the mediating role of angiopoietin-1 receptor level between phlebitis and multiple myeloma was explored by two-step Mendelian randomization analysis. Inverse variance weighting (IVW) was used as the main MR Analysis method, MR-Egger regression was used to test horizontal pleiotropy, and sensitivity analysis was performed by leave-one-out test. The MR Results were visualization by scatter plot, forest plot and funnel plot. Results There is no independent causal relationship between phlebitis and the occurrence of multiple myeloma.(OR=0.999, 95% CI: 0.997-1.003, P=0.638).The risk of multiple myeloma increased when phlebitis occurred (OR=1.005, 95% CI: 1.001-1.009, P=0.009). The level of angiopoietin-1 receptor increased the risk of phlebitis (OR=1.053, 95% CI: 1.017-1.092, P=0.004). The risk of multiple myeloma increased with the increase of angiopoietin-1 receptor level (OR=1.006, 95% CI: 1.002-1.010, P=0.004).Conclusion Phlebitis may increase the risk of multiple myeloma and angiopoietin-1 receptor levels may be a potential mediator between phlebitis and multiple myeloma.