Abstract Aims Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with acute PE. Methods and results We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [β 0.32 (0.26–0.38), P < 0.001]. During the same period, in-hospital case fatality rates decreased from 20.4% to 13.9% [β −0.51 (−0.52 to −0.49), P < 0.001]. The overall proportion of patients treated with systemic thrombolysis increased from 3.1% in 2005 to 4.4% in 2015 [β 0.28 (0.25–0.31), P < 0.001]. Thrombolysis was associated with lower in-hospital mortality rates in patients with haemodynamic instability, both in those with shock not necessitating cardiopulmonary resuscitation (CPR) or mechanical ventilation [odds ratio (OR) 0.42 (0.37–0.48), P < 0.001], and in those who underwent CPR [OR 0.92 (0.87–0.97), P = 0.002]. This association was independent from age, sex, and comorbidities. However, systemic thrombolysis was administered to only 23.1% of haemodynamically unstable patients. Conclusion Although the proportion of PE patients treated with systemic thrombolysis increased slightly in Germany between 2005 and 2015, only the minority of haemodynamically unstable patients currently receive this treatment. In the nationwide inpatient cohort, thrombolytic therapy was associated with reduced in-hospital mortality rates in PE patients with shock, and also in those who underwent CPR.