Mobilization of patients supported on extracorporeal membrane oxygenation (ECMO)—especially with femoral cannulas—presents unique challenges. This single-center retrospective cohort study aims to assess the efficacy and safety of mobilizing these patients using a specialized, fully vertically tilting bed. All adult (≥ 18 years) patients receiving ECMO for greater than or equal to 48 hours from January 2018 to December 2019 who were placed on the tilt bed were compared with those who were not. Of the 152 included patients, 24 (15.8%) were placed on the tilt bed and underwent 124 physical therapy (PT) sessions, whereas 42 (32.8%) others participated in 183 non-tilt bed PT sessions. Tilt bed patients were younger (46.4 [38.1–48.9] vs. 55.9 [42.8–65.8] years, p = 0.002) and more likely to be on ECMO as a bridge to decision/transplant (54.1% vs. 20.3%, p < 0.001). Despite significantly longer durations of ECMO support (20 [13–30] vs. 8 [4–16] days, p < 0.001), tilt bed patients achieved mobility milestones at comparable timepoints following decannulation (standing: 3 [2–6] vs. 5 [3–11] days, p = 0.08; ambulation: 10 [5–17] vs. 7 [3–20] days, p = 0.81). Minor adverse events occurred during 15.2% of tilt bed sessions with no serious adverse events. Tilt beds may provide a safe and effective modality to facilitate the mobilization of ECMO patients.