There remains limited information about the prevalence and outcomes of hemodynamic unstable patients with acute pulmonary embolism (PE). We performed a systematic review and meta-analysis of prospective registries that enrolled patients with acute PE to assess the prevalence and prognostic significance of hemodynamic instability for the primary outcome of short-term all-cause mortality, and the secondary outcome of short-term PE-related mortality. We also assessed the association between use of thrombolytic therapy versus no use and short-term outcomes in the subgroup of unstable patients. We used a random-effects model to pool study results; and I 2 testing to assess for heterogeneity. The authors’ search retrieved 4 studies that enrolled 1,574 patients with unstable PE (1,574/40,363; 3.9%; 95% confidence interval [CI], 3.7% to 4.1%). Hemodynamic instability had a significant association with short-term all-cause mortality (odds ratio [OR], 5.9; 95% CI, 2.7 to 13.0; I 2 = 94%), and with PE-related death (OR, 8.2; 95% CI, 3.4 to 19.7). In unstable patients, thrombolytic therapy was associated with reduced odds of short-term all-cause mortality (OR, 0.69; 95% CI, 0.49 to 0.95), and PE-related death (OR, 0.66; 95% CI, 0.45 to 0.97). In conclusion, hemodynamic instability significantly increased the risk of death shortly after PE diagnosis. Use of thrombolytic therapy was associated with significantly reduced short-term mortality.