Severe respiratory failure is frequently complicated by right ventricular dysfunction (RVD), which occurs in 20–50% of cases. In patients on venovenous extracorporeal membrane oxygenation (VV ECMO) with refractory RVD, conversion to venopulmonary (VP) ECMO can provide additional mechanical support. This study evaluates the impact of VV to VP ECMO conversion on mortality and end-organ dysfunction in severe respiratory failure. A retrospective cohort study of 19 adult patients on VV ECMO who were converted to VP ECMO was performed. Outcomes included in-hospital mortality, resolution of acute kidney injury (AKI), pressor requirements, ventilator and ECMO parameters, and ECMO support duration. Venopulmonary ECMO conversion facilitated AKI resolution in 62.5% of patients with pre-conversion AKI (5/8) and was associated with liberation from continuous renal replacement therapy in 40% of patients (2/5). Conversion resulted in reduced pressor requirements (7/9, 78%), ECMO flows (15/19, 79%), sweep gas flow (12/19, 63%), ECMO fraction of inspired oxygen (FiO₂; 5/19, 26%), and ventilator FiO₂ (3/19, 16%). Venopulmonary ECMO conversion facilitated sedation weaning in 10 patients (53%) which was previously not tolerated due to desaturation events on VV ECMO. Overall, VP ECMO conversion was associated with improved oxygenation, hemodynamic stability, and end-organ function in the majority of patients.