OBJECTIVE: The goal of this study was to inform public health policy which can reduce Colombia’s estimated infant mortality rate (IMR), 17.78 deaths for 1000 live births (2011), by lowering preventable first day mortality (PFDM). STUDY DESIGN: This study combined a time series analysis, using a linear regression method, for the period 2001-2012 with a cross-sectional analysis, using odds ratios and bi-variate methods, for the year 2012 to study first day mortality (FDM) and PFDM classified by biological, socio-economic, and medical correlates. METHODS: The study examined the trends for 2001-2012 in Colombia’s infant mortality rate per 1000, and in the relative significance of PFDM by cause. It established the relative odds of PFDM for 2012 by major risk categories, defined by birthweight and gestational age, and within those by biological, sociodemographic risk factors or groups and by potential access to and use of care. Then, the study established the major causes of PFDM within major risk categories and groups. RESULTS: Between 2001 and 2012, the average annual rate of FDM declined by 6.30%, while overall infant mortality only declined by 4.20%. Yet, in 2012, 37.04% of FDM was preventable by using proper pregnancy control (7.00% of total preventable), proper care during childbirth (37.20%), and handling causes associated with late diagnosis and treatment (55.80%). PFDM is primarily a socio-economic phenomenon, even among normal weight and gestational age newborns, who account for 32.73% of PFDM due to improper management of pregnancy and delivery among lower socio-economic and outlying populations, specifically in rural areas and among members of the inferior subsidised social insurance regime. CONCLUSION: From efficacy and probable cost effectiveness perspectives, intervention priority should be given to handling babies with normal gestation age and birthweight, and then to babies with very low gestation age and birthweight. At the same time, more prenatal visits could lead to fewer very high-risk situations at the outset. In view of the Colombian regulation to the contrary, the use of foetal monitoring and echography methods by all general practitioners should be considered. They should be trained accordingly. Policies should focus on members of the underprovided subsidised health insurance regime, rural areas, young, low-educated and single mothers during pregnancy, mainly delivery.