Catheter-directed interventions (CDIs) have been increasingly used for selected patients with acute intermediate-risk (submassive) pulmonary embolism (sPE) to prevent decompensation, mortality, and potentially long-term sequelae. The purpose of the present study was to determine whether the choice of anesthetic during these interventions has an effect on the postprocedural outcomes. Patients who had undergone CDI for acute sPE from 2009 to 2019 were identified and grouped according to the intraprocedural use of propofol. The primary outcome was in-hospital intra- or postprocedural major adverse events, defined as the need for intubation, progression to massive pulmonary embolism, and in-hospital death. Major bleeding events (ie, intracerebral hemorrhage, transfusion of ≥2 U, the need for reintervention) were also assessed. Multivariate logistic regression analysis was used to evaluate the predictors of the studied outcomes. During the study period, 340 patients (age, 58.74 ± 15.22years; 51.2% men) had undergone CDI for sPE (85 standard thrombolysis, 229 ultrasound-assisted thrombolysis, 26 suction thrombectomy). Propofol had been used for 36 patients (10.6%); the remaining 304 patients (89.4%) had received midazolam plus fentanyl, morphine, or hydromorphone for anesthesia. The baseline characteristics of both groups were similar, except for age, hypertension, American Society of Anesthesiologists class, and procedure type, with ultrasound-assisted thrombolysis the predominant procedure for the no-propofol group (74%). Overall, 18 patients had experienced ≥1 events of the composite outcome (ie, 10 intubations, 11 decompensations, 2 surgical conversions, 3 deaths). The propofol group had a significantly greater adverse event rate (13.8%; n= 5) compared with the no-propofol group (4.2%; n = 13; P= .015). On multivariate analysis, propofol was still a predictive factor for adverse events (odds ratio, 3.79; 95% confidence interval, 1.11-12.93; P= .03). A total of 16 patients had experienced major bleeding or other procedure-related events, including stroke in 4 (1.17%), coronary sinus perforation in 1, tricuspid valve rupture in 1, and the need for transfusion in 10 patients. The type of intervention (ie, standard thrombolysis, ultrasound-assisted thrombolysis, suction thrombectomy) was not a predictive factor for any studied outcome. CDIs are low-risk procedures with minimal postoperative morbidity and mortality in the setting of acute sPE. However, the use of propofol for intraprocedural sedation should be avoided because it can have detrimental effects.