ABSTRACT: RATIONALE:To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). OBJECTIVES:To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors. METHODS:After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS:Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other countries. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: 5 injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into L pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one patient had chronic obstructive pulmonary disease with small subpleural blebs and poor collapse, confirmed by CT. Two uDCDDs with MIs were suitable but not transplanted: no consented recipient from one large blood type B uDCDD, and the senior surgeon was unavailable to transplant suitable lungs from a uDCDD and did not allow the transplant. CONCLUSIONS:The objective was not met: no lungs from uDCDDs were transplanted. uDCDDs can be a source of lungs for transplant. Resolving logistical challenges and better use of first-person authorization, allowing organ recovery without next-of-kin consent or knowledge of death, could increase yield. Donor medical problems were higher than expected and may limit the effect of uDCDDs on the lung donor pool. CLINICAL TRIAL REGISTRATION:NCT01615484.