This study reports the incidence, clinical profile and mortality for acute pulmonary embolism (PE) patients in the Danish population in four eras from 2004 to 2014. Patients admitted with first-time acute PE from 2004 through 2014 were identified from national patient registries classified according to the International Classification of Diseases, 10th edition, World Health Organization. A total of 30,275 patients from a population of 4,301,673 adult residents aged 18 years or older were diagnosed with first-time acute PE, corresponding to an incidence of 64 (95% confidence interval: 61–66) per 100,000 adult residents per year. Throughout the study period, PE incidence increased from 45 to 83 per 100,000 adult residents. Age at disease onset also increased during the study period, rising from 67.1 to 68.0 ( p = 0.002). Cancer was the most frequent concomitant diagnosis, with an incidence of 15.9%. Thoracic computed tomography and referral to specialized cardiac centres increased significantly throughout the study period. The 30- and 90-day mortality rates decreased between 2004 and 2014 from 17 to 11% and from 23 to 18% ( p < 0.00), respectively. The 5-year mortality risk was reduced when comparing Era IV (2012–2014) with Era I (2004–2005), with a hazard ratio of 0.93 ( p = 0.01). In Denmark, the annual incidence of acute PE has increased during the past decade from 45 to 83 per 100,000 adults with a significant decrease in both short- and long-term mortalities. In recent years, patients were more likely to be investigated with modern diagnostics and referred to cardiac centres for specialized treatment.