The incidence of thromboembolic events is high as a result of disease, disease-related complications, and therapy in multiple myeloma (MM). In patients with hematologic tumors, impaired fibrinolysis may be present and may contribute to the development of thrombotic complications. Therefore, we designed a study to investigate fibrinolytic activity in MM. We compared plasma levels of interleukin (IL)-6, C-reactive protein (CRP), IL-1β, IL-11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow-up period of 7 months in our myeloma group. Results are given as mean (median, range). Plasma levels of IL-6 (8.27 ± 0.74 [9.65, 0.90–13.32] pg/mL versus 2.64 ± 0.66 [1.80, 0.10–11.86] pg/mL, P < 0.001), CRP (45.57 ± 9.92 [21.00, 1.34–330.00] mg/L versus 1.96 ± 0.50 [1.05, 0.19–8.03] mg/L, P < 0.001), PAI-1 (7.40 ± 0.67 [5.57, 2.40–31.80] IU/mL versus 4.73 ± 0.65 [3.60, 2.32–11.00] IU/mL, P < 0.01), GFC score (1.90 ± 0.02 [2, 1–3] versus 2.50 ± 0.14 [3, 1–3], P < 0.001) were increased compared with controls. In patients with MM, the level of IL-6 was positively correlated with CRP (r = 0.66, P < 0.001), IL-1β (r = 0.29, P < 0.05), and PAI-1 (r = 0.35, P < 0.01) and negatively correlated with GFC (r = −0.37, P < 0.01). CRP level was positively correlated with plasma PAI-1 level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = −0.44, P < 0.001). A significant negative correlation between PAI-1 level and GFC (r = −0.75, P < 0.001) was also detected. IL-1β levels were negatively correlated with tPA level (r = −0.26, P < 0.05). These results suggest that patients with myeloma have a decreased fibrinolytic activity mainly because of increased PAI-1 activity. In MM, increased PAI-1 activity seems to be related with elevated IL-6 level. MM should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic activity. Achieving a plateau by means of conventional chemotherapies does not improve the decreased fibrinolytic activity. Am. J. Hematol. 74:231–237, 2003. © 2003 Wiley-Liss, Inc.