Background: Traditionally, mechanical thrombectomy performed for pulmonary embolism (PE) necessitates the utilization of iodinated contrast. Intravascular ultrasound (IVUS) has been used as a diagnostic and therapeutic modality in the management of acute high and intermediate-risk PE. Recently, with the shortage of contrast supplies and the considerable incidence of contrast-induced acute kidney injury (CI-AKI), other safer and more feasible IVUS methods have become desirable. The purpose of this systematic review was to evaluate the importance of IVUS in patients with PE undergoing thrombectomy. Methods: Medline/PubMed, Embase, Scopus, and Google Scholar were searched for review studies, case reports, and case series. Clinical characteristics, outcomes and the usage of IVUS-guided mechanical thrombectomy during the treatment of acute high and intermediate-risk PE were examined in a descriptive analysis. Results: In this systematic review, we included one prospective study, two case series, and two case reports from July 2019 to May 2023. A total of 39 patients were evaluated; most were female (53.8%). The main presenting symptoms were dyspnea and chest pain (79.5%); three patients (7.9%) presented with syncope, one with shock and one with cardiac arrest. Biomarkers (troponin and BNP) were elevated in 94.6% of patients. Most patients (87.2%) had intermediate-risk PE, and 12.8% had high-risk PE. All patients presented with right-heart strain (RV/LV ratio ≥ 0.9, n = 39). Most patients (56.4%) had bilateral PE. Mechanical thrombectomy was performed using IVUS without contrast utilization in 39.4% of the patients. After the initial learning curve, contrast usage decreased gradually over time. There was a significant decrease in the composite mean arterial pressure immediately following IVUS-guided thrombectomy from 35.1 ± 7.2 to 25.2 ± 8.3 mmHg (p < 0.001). Post-procedure, there was no reported (0%) CI-AKI, no all-cause mortality, no major bleeding, or other adverse events. There was a significant improvement in symptoms and RV function at the mean follow-up. Conclusions: New evidence suggests that IVUS-guided mechanical thrombectomy is safe, with visualization of the thrombus for optimal intervention, and reduces contrast exposure.