BackgroundBreastfeeding has a great effect on health promotion and disease prevention in premature infants. However, various factors affect the success of breastfeeding process in mothers. The present study aims to: a) explain breastfeeding experiences; b) assess the factors affecting breastfeeding self-efficacy; and c) present a guideline for promoting breastfeeding in mothers of premature infants.MethodsThis mixed-methods study with a sequential explanatory design consisted of three phases. The first phase is qualitative study to explore the breastfeeding experiences in mothers of premature infants. In this phase, the subjects will be selected through purposive sampling; moreover, in-depth individual interviewing will be used for data collection. Finally, the conventional content analysis approach will be employed for data analysis. The second phase is quantitative and will be used a cross-sectional approach to assess the association of the social determinants of health with breastfeeding self-efficacy in mothers of premature infants. In this phase, the multistage cluster sampling method will be used to select 360 subjects who will be visited healthcare centers in Tabriz, Iran. The third phase focused on developing strategies to increase the ability of mothers to breastfeed their premature infants, using the qualitative and quantitative results of previous phases, a review of the related literature, and the nominal group technique will be performed among experts.DiscussionThe present research is the first study that investigated the experiences of breastfeeding and factors influencing breastfeeding self-efficacy in mothers of premature infants. For the purposes of the study, the mixed methods approach will be used which aimed to develop strategies for the improvement of healthcare services in this regard. It is worth noting that there is no strategic guideline in Iran’s healthcare system for the improvement of breastfeeding, especially regarding mothers of premature infants. Therefore, it is hoped that the strategy proposed in the current study can lead to improvements in this regard.Ethical codeIR.TBZMED.REC.1398.100.