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Attitudes of physicians toward neonates with poor prognosis greatly influence their decisions regarding the course of treatment and care. The present study aimed to investigate factors contributing to attitudes of medical practitioners toward poor prognosis neonates. This was a cross-sectional, descriptive-analytic study. Questionnaires for assessing subjects’ attitudes toward care of very poor prognosis neonates were administered to all neonatologists, pediatricians, neonatology assistants, and pediatric residents (a total of 88 individuals) working in the NICUs of Imam Khomeini Hospital. Participants’ attitudes were determined through analysis of responses to seven questions on a 5-point Likert scale ranging from “strongly agree” to “strongly disagree”. Presence of anomalies incompatible with an acceptable quality of life, birth weight, gestational age, responses to neonatal diagnostic tests, certain types of diseases, parental marital status and practitioner predictions about patient prognosis were the factors contributing to practitioners’ attitude (P-value < 0.005). However, no significant relationship was found in connection with religious beliefs, socioeconomic status, opinions of consulting physicians, hospital treatment protocols, standards of the Association of Neonatal Physicians, and ethics committee expectations (P-value > 0.005). It can be concluded that the attitudes of practitioners toward intensive care of poor prognosis neonates is determined by the medical condition of the neonate rather than socio-demographic characteristics.