Controlled donation after circulatory death (cDCD) occurs after a decision to withdraw life-sustaining treatment (WLST) and subsequent family approach and approval for donation. We currently lack data on factors that impact the decision-making process on WLST and whether time from admission to family approach, influences family consent rates. Such insights could be important in improving the clinical practice of potential cDCD donors. In a prospective multicenter observational study, we evaluated the impact of timing and of the clinical factors during the end-of-life decision-making process in potential cDCD donors. Characteristics and medication use, of 409 potential cDCD donors admitted to the intensive care units (ICU), were assessed. End-of-life decision-making was made after a mean time of 97 h after ICU admission and mostly during the day. Intracranial hemorrhage or ischemic stroke and a high APACHE IV score were associated with a short decision-making process. Preserved brainstem reflexes, high Glasgow Coma Scale scores or cerebral infections were associated with longer time to decision-making. Our data also suggest that the organ donation request could be made shortly after the decision to stop active treatment and consent rates were not influenced by day- or nighttime or by the duration of the ICU stay.