Objective To clarify the process of end-of-life decision-making in culturally different neonatal intensive care units (NICUs). Study design Review of medical files of newborns >22 weeks gestation who died in the delivery room (DR) or the NICU during 12 months in 4 NICUs (Chicago, Milwaukee, Montreal, and Groningen). We categorized deaths using a 2-by-2 matrix and determined whether mechanical ventilation was withdrawn/withheld and whether the child was dying despite ventilation or physiologically stable but extubated for neurological prognosis. Results Most unstable patients in all units died in their parents' arms after mechanical ventilation was withdrawn. In Milwaukee, Montreal, and Groningen, 4% to 12% of patients died while receiving cardiopulmonary resuscitation. This proportion was higher in Chicago (31%). Elective extubation for quality-of-life reasons never occurred in Chicago and occurred in 19% to 35% of deaths in the other units. The proportion of DR deaths in Milwaukee, Montreal, and Groningen was 16% to 22%. No DR deaths occurred in Chicago. Conclusions Death in the NICU occurred differently within and between countries. Distinctive end-of-life decisions can be categorized separately by using a model with uniform definitions of withholding/withdrawing mechanical ventilation correlated with the patient's physiological condition. Cross-cultural comparison of end-of-life practice is feasible and important when comparing NICU outcomes. (J Pediatr 2010; 156: 33-7).