Ultrasound-assisted catheter directed thrombolysis (USAT) has been shown to improve hemodynamic function and reduce bleeding complications in patients with acute massive or submassive pulmonary embolism. We performed a meta-analysis to better evaluate the efficacy and safety of USAT. We conducted an extensive literature search in PUBMED, MEDLINE, and EMBASE databases from January 1, 2008 to December 31, 2018. Efficacy outcomes of interest were pulmonary artery systolic pressure, mean pulmonary pressure, ratio of right ventricular to left ventricular diameter, cardiac index, tricuspid annular plane systolic excursion, Miller Index Score, and Qanadli Score. Safety outcomes were in-hospital mortality, long-term mortality, major and minor bleeding complications, and recurrent pulmonary embolism. Meta-analysis was performed using Cochrane Collaboration Review Manager (version 5.1). Effect size was estimated using random effects model, with 95% confidence intervals (CIs). Twenty-eight studies (n = 2,135) met inclusion criteria. Compared with pretreatment parameters, post-USAT was associated with a reduction in the mean Miller Index Score and Qanadli Score by 10.55 (95% CI −12.98 to −8.12) and 15.64 (95% CI −19.08 to −12.20), respectively. Cardiac index and tricuspid annular plane systolic excursion improved by 0.68 L/m2 (95% CI 0.49 to 0.87) and 3.68 mm (95% CI 2.43 to 4.93), respectively. Pulmonary artery systolic pressure and mean pulmonary pressure after therapy were reduced by a mean difference of 16.69 mm Hg (95% CI −19.73 to −13.65) and 12.13 mm Hg (95% CI −14.67 to −9.59) respectively. The right ventricular to left ventricular diameter dimension ratio decreased by 0.35 (95% CI −0.40 to −0.30) after therapy. In-hospital mortality in patients who underwent USAT was 2.9%, and total long-term mortality was 4.1%. Major and minor bleeding complications were seen in in 5.4% and 6.0% of patients, respectively. Recurrent events occurred in 0.2% of patients after USAT. In conclusion, USAT is a safe and effective procedure associated with significant hemodynamic and clinical improvement in patients with massive and submassive pulmonary embolism.