AbstractSyncope in pulmonary embolism (PE) could be the first sign of haemodynamic compromise. We aimed to investigate pathomechanisms of syncope and its impact on mortality. For this study, patients (aged ≥ 18years) were selected by screening the German nationwide inpatient sample for PE and stratified included patients by syncope (2011–2014). We analysed predictors of syncope in haemodynamically stable PE. Impact of syncope on in-hospital mortality in haemodynamically stable and unstable PE and benefit of systemic thrombolysis in haemodynamically stable PE with syncope (PE + Syncope) were analyzed. The German nationwide inpatient sample comprised 293,640 (84.9%) haemodynamically stable and 52,249 (15.1%) unstable PE patients; among them 2.3% had syncope. Right ventricular dysfunction (RVD) was a key predictor for syncope. In-hospital mortality-rate was lower in haemodynamically stable (6.4% vs. 7.6%, P < 0.001) and unstable PE + Syncope than in PE−Syncope (48.4% vs. 55.5%, P < 0.001) with reduced risk for in-hospital death in stable (OR 0.68 (95%CI 0.61–0.75), P < 0.001) and unstable (OR 0.69 (95% CI 0.62–0.78), P < 0.001) inpatients independent of age and sex. Haemodynamically stable PE + Syncope patients were more often treated with systemic thrombolysis (3.1% vs. 2.1%, P < 0.001). Systemic thrombolysis was associated with reduced in-hospital mortality in haemodynamically stable PE + Syncope (1.9% vs. 6.6%, P = 0.004) independently of age, RVD and tachycardia (OR 0.30 (95%CI 0.11–0.82), P = 0.019). In conclusion, in-hospital mortality was 6.4% in haemodynamically stable PE + Syncope. Haemodynamically stable PE + Syncope patients were more often treated with systemic thrombolysis and showed a trend to improved survial.