OBJECTIVE To evaluate the clinical factors, as well as weight gain, in a group of pregnant women, associating them with fetal macrosomia in a public institution in Antioquia, Colombia, from 2010-2017.METHODS A case-control study, using secondary information registries. Cases were defined using newborn weight of ≥ 4000g, while controls were defined as newborn weight between 3000–3999g. A proportion ratio (PR) was established to evaluate factors associated with macrosomia, and a generalized linear model (GLM) of Poisson regression with robust variance was used to evaluate the aspects that best explained macrosomia in the neonate.RESULTS 122 pregnant women participated in the study, of which 611 were cases and 61 were controls. Of the participants, 44.3% had pre-pregnancy overweight and 48.4% had excess gestational weight gain. Statistically significant differences were found between the groups in the following variables: pre-pregnancy BMI (p = 0.004), gestational weight gain (p = 0.000), gestational diabetes (p = 0.000), and type of delivery (p = 0.004). According to the regression model, a macrosomic newborn is 3.5 times more likely in women with excessive gestational weight gain (95%CI 1.78-7.18) and twice more likely in women who have gestational diabetes (95%CI 1.51-2.76). Of women with pre-pregnancy excess weight, 63% had excess gestational weight gain.CONCLUSIONS Within this cohort, pre-pregnancy BMI, excess weight gain in pregnancy, and the presence of gestational diabetes were associated with an increased risk of neonatal macrosomia. pre-pregnancy BMI and weight gain in pregnancy are modifiable risk factors that are responsive to nutrition interventions, which can minimize adverse perinatal outcomes.