Background: Within their first year of diagnosis, as many as 1 in 3 multiple myeloma (MM) patients will experience a venous thromboembolism (VTE). The International Myeloma Working Group (IMWG) has issued thromboprophylaxis guidelines that stratify patients into low or high risk for thrombosis and subsequently recommend aspirin (ASA, low risk) versus low molecular weight heparin (LMWH) or therapeutic warfarin ( high risk). We conducted a matched case-control study to determine if these guidelines are used in practice, and when they are, if they result in fewer VTEs for MM patients. Methods: The Healthcare Enterprise Repository for Ontological Narration (HERON) database was used to identify case patients with MM and a VTE. Controls, patients with MM who had not experienced a VTE, were matched (~ 1:3) to the cases based on gender, age (+/- 5 years), and time of diagnosis (+/- 5 years). Patient charts were manually extracted to identify treatment history, disease history, and risk factors for VTE. We then evaluated the distribution of risk of VTE per the IMWG guidelines with use of prophylactic anticoagulation. Using conditional logistic regression, we examined an association between risk of VTE, medications use, and the interaction between risk category for the matched patients at the time of diagnosis and at the time of the VTE. Results: There were a total of 297 patients in the final cohort, 86 cases and 211 controls. The median time from diagnosis to VTE was 952 days. Patients with a higher risk of VTE were more likely to be on LMWH or warfarin versus ASA or no prophylaxis (p < .001). We did not find an association between risk category or prophylactic medication with the rate of VTE when considering baseline risk factors. The risk category of case patients changed to a higher risk group over time and this was associated with a higher risk of clot (p = .06). Conclusions: Our data suggest that VTE in MM may occur later in the disease process than has historically been reported. While we were unable to validate the IMWG recommendations for thromboprophylaxis at diagnosis, our results suggest that the risk for VTE may change over time and that patient’s require ongoing assessment of VTE risk and thromboprophylaxis throughout the disease course.