AimThe aim of this study was to explore factors affecting adaptation to the role of motherhood in mothers of preterm infants admitted to the neonatal intensive care unit. BackgroundTransition to motherhood often causes significant issues in terms of adaptation to the role of motherhood. The main factors leading to parental stress, especially in the neonatal intensive care unit, have shown that the greatest source of stress is the loss of women's role as mothers. DesignIt was a qualitative study with content analysis approach. MethodsSemi-structured in-depth interviews were used for data collection. Interviews were conducted with 17 mothers of preterm infants (under 36weeks) who had been hospitalized for at least one week in the neonatal intensive care unit. Purposive sampling with maximum diversity was used to recruit mothers in Kermanshah province (west of Iran). Data was collected during 2013-2014. Interviews were recorded and transcribed verbatim. Data were analysed using conventional content analysis. FindingsExplanation of the mothers' perspective towards factors affecting adaptation to the role of motherhood led to two main categories of individual factors (emotional distress, self-efficacy, interaction and alienation) and social factors (support, prejudice). ConclusionAdaptation to the role of motherhood can be promoted through supporting mothers of preterm infants, empowering them and increasing their self-efficacy, to eliminate negative factors and emotions.