Objectives. In neonatal intensive care units (NICUs), difficult decisions about care and withdrawal of treatment sometimes have to be taken by parents and healthcare workers, especially when the infant will probably have a poor developmental outcome. Only one previous study conducted in South Africa investigated whether preferences in this regard differ between these groups. We aimed to acquire more information on the issue. Design. A comparative cohort study comprising separate groups. Setting. Neonatal units of Universitas Academic and Pelonomi Regional hospitals. Subjects. Mothers of very low-birth-weight (VLBW) babies and children with multiple disabilities; paediatricians (including registrars) and nurses working in these units. Outcome measures. The preferences for developmental outcomes were compared between four groups: nurses, paediatricians, mothers of VLBW infants, and mothers of babies with multiple disabilities. Different scenarios were illustrated, and questionnaires were used to obtain the opinions on active treatment for babies with a poor developmental outcome. Results. When asked whether doctors should attempt to save premature babies, even with a more than 50% chance of being handicapped, 100% of mothers agreed, as opposed to 23% of paediatricians. Similar results were obtained when respondents were asked whether they would prefer to have a severely handicapped child rather than no children at all. Seventy per cent of mothers of VLBW babies indicated that parents are the most important stakeholders in NICU decision making. Conclusions. Doctors may underestimate mothers’ capacity to cope with handicapped children. The opinion and perspectives of mothers are therefore important factors in NICU decision making.