Approximately 3.3 million (41 %) of global child deaths occur among children in the first 28 days oflife (the neonatal period). Neonatal death reduction is imperative to achieving the 4th millennium development goal (MDG-4) which seeks to reduce global child deaths by two-thirds its levels in 1990 come 2015. Three direct causes: infections, asphyxia, and prematurity or low birthweight and its complications account for approximately 80% of these deaths, majority of which are preventable. Infection is the single most important cause in about a third (and up to half in high mortality settings) of all neonatal deaths. However, care seeking for sick newborns is generally poor and besieged by myriads of barriers with many newborn deaths occurring at home with no contact with health providers. Trials in south Asia have shown that prompt detection and treatment of newborn infections coupled with effective preventive measures can significantly reduce newborn deaths. The Ghana Newhints home visits cluster randomised controlled trial (CRT) is the first trial in sub-Saharan Africa to evaluate the impact of a community-based strategy on newborn care practices and neonatal mortality.