Background: Venous thromboembolism (VTE) has major clinical and public health impact. However, only sparse data on calendar time trends in incidence from unselected populations reflecting current clinical practice are available. Objectives: To examine temporal trends in the incidence and characteristics of patients hospitalized with first-time VTE in Denmark between 2006 and 2015. Patients/Methods: Using nationwide health care registries, we calculated yearly hospitalization rates for first-time VTE from 2006 to 2015. The rates were standardized to the age and sex distribution in 2006. Based on the hospitalization and prescription history of each patient, we assessed the risk profile and evaluated changes over time. Results: We identified 67,426 patients with a first-time VTE hospitalization. The age- and sex-standardized incidence rate increased from 12.6 (95% CI: 12.3–12.9) per 10,000 person years at risk in 2006 to 15.1 (95% CI: 14.7–15.4) in 2015, corresponding to an increase of 19.8%. The increase was due to a 73.9% increase in the standardized incidence rate of pulmonary embolism (PE), whereas no increase was observed for deep vein thrombosis. The risk profile changed with an increasing proportion of elderly patients and patients with comorbidity (proportion of patients with a Charlson's Comorbidity Index score of ≥1). Conclusions: The hospitalization rate of first-time VTE, and particularly PE, has increased substantially within the last decade in Denmark. In addition, the risk profile of the VTE population has changed with more elderly and more patients with comorbidity being diagnosed. Further efforts are warranted to explore the changes in VTE epidemiology and the clinical implications.