Preterm birth has been increased over the last two decades, thus leading to higher admissions of preterm infants to the neonatal intensive care units (NICUs). The design of NICUs may have several consequences for the health of infants, parents, and staff. In addition, it has gone through numerous changes in recent years, including the single-family room (SFR). The purpose of this study was to investigate the effects of using SFRs in the NICUs on the environmental (outcomes related to NICU environmental features) and clinical outcomes of the infants. Further, the present systematic review study was based on English papers about utilizing SFRs in the NICUs published during 2012-17. The papers were collected by searching the keywords “ neonatal intensive care unit” , “ single-family room” , “ preterm infants” , “ parents’ perspective” , “ staff’ s perspective” , “ infant outcomes” , and “ open-ward care unit” in ISI, Scopus, PubMed, Science Direct, Google Scholar, Magiran, and OVID database. The findings showed that applying SFRs improves clinical and environmental outcomes and that the staff and parents have a positive attitude toward this method. Besides, it costs the same as or even in some models less than the open-ward method and is considered a cost-effective method. Although a consensus may not be achieved on some issues such as maternal stress, language and motor development, intellectual maturation, and to some extent nurses’ satisfaction, in general, using the SFR in the NICUs enhances clinical and environmental outcomes and there is a positive attitude towards this method.