PurposeTo compare changes in hemoglobin (HB) following catheter-directed thrombolysis (CDL) versus large-bore aspiration thrombectomy (LBAT) of acute pulmonary embolism (PE). Materials and MethodsA single-center retrospective review of patients with acute high- and intermediate-risk PE treated with CDL or LBAT between December 2009 and September 2023 was performed. The LBAT group was divided according to usage of an autotransfusion device (ATD). There were 166 patients in the CDL group (56 years ± 15). LBAT patients were treated without (LBAT, n = 58, 61 years ± 16) or with (LBATw, n = 47, 62 years ± 15) an ATD. Endpoints included change in HB between preprocedural and postprocedural measurements, the 7-day postprocedural nadir (low point), and adverse events (AEs). ResultsThe mean HB changes between preprocedural and postprocedural measurements in the CDL, LBAT, and LBATw groups were −1.3 g/dL ± 1.3, −1.6 g/dL ± 0.98, and −1.1 g/dL ± 0.9, respectively (P = .098). The mean HB changes to the 7-day postprocedural nadir in the CDL, LBAT, and LBATw groups were −1.7 g/dL (SD ± 1.4), −2.4 g/dL (SD ± 1.3), and −1.8 g/dL (SD ± 1.3), respectively (P = .008). The minor hemorrhagic AE rates were 3.6% in the CDL group, 12.1% in the LBAT group, and 14.9% in the LBATw group (P = .010). There was no significant difference in moderate (P = .079) and major (P = .529) hemorrhagic AEs between the groups. There were no procedure-related mortalities. ConclusionsThe use of LBAT without ATD resulted in a significant decrease in HB to the 7-day postprocedural nadir compared with CDL or LBAT with ATD. This did not translate into significantly higher transfusion rates or moderate or major hemorrhagic events. Findings suggest that the decision between CDL and LBAT should not be based solely on the expected blood loss consideration.