Abstract Objectives: To compare intraoperative patterns among patients based on their primary pulmonary disease (cystic fibrosis [CF], chronic obstructive pulmonary disease [COPD]/emphysema [CE], and pulmonary fibrosis [PF]) during double- lung transplantation. The following 3 major outcomes were reported: blood transfusion, extracorporeal membrane oxygenation (ECMO) management, and the possibility of immediate extubation at the end of surgery. Design: Retrospective analysis of a prospectively maintained database, including donor and recipient characteristics and intraoperative variables. Setting: Foch Hospital, Suresnes, France (academic center performing 60-80 lung transplantations per year). Participants: Patients who underwent double- lung transplantation from 2012-2019. Patients with retransplantation, multiorgan transplantation, or surgery performed with cardiopulmonary bypass were excluded. Interventions: None. Measurements and main results: Two hundred forty-six patients had CF, 117 had CE, and 66 had PF. No patient had primary pulmonary arterial hypertension. Blood transfusion was higher in the CF group than in the other 2 groups (red blood cells [p < 0.001], fresh frozen plasma [p = 0.004]). The CF and CE groups were characterized by a lower intraoperative requirement of ECMO (p = 0.002), and the PF group more frequently required postoperative ECMO (p < 0.001). CF and CE patients were more frequently extubated in the operating room than were PF patients (37.4%, 50.4%, and 13.6%, respectively; p < 0.001). Conclusions: Intraoperative outcomes differed depending on the initial pathology. Such differences should be taken into account in specific clinical studies and in intraoperative management protocols.