There is enough scientific evidence indicating a relationship between particulate matter in ambient air and health. Since at a global scale there is an important number of people exposed to this pollutant, studies have focused on evaluating its possible effects on human population. Aburrá Valley Metropolitan Area (AMVA), in Antioquia-Colombia, is a region with about 3,909,729 inhabitants (2018), where 79% of PM2.5 present in the atmosphere is emitted by motor vehicles, with 1534 ton/year (AMVA, 2018). In the last decade, monitoring stations have reached daily mean concentrations of 113 μg/m3, which is 226% in excess of the maximum permissible daily level established at 50 μg/m3 by Colombian regulations (AMVA 2016; MinAmbiente, 2017). The object of the study was to evaluate the impact of PM2.5 concentrations in cases of premature mortality of urban population. To this end, the BenMap-CE v.1.1 model was used, together with Krewski et al. (2009) Health Impact functions to evaluate associations with adult mortality (>30 years of age) due to All Causes (AC)—including natural and non-natural—(ICD-10: A00-Y98), Ischemic Heart Disease (IHD) (ICD-10: I20–I25) and LungCancer (LC) (ICD-10: C34); and Woodruff et al. (2006) functions to explore associations with child mortality (population 0–1 year of age) due to All Causes (AC)—including natural and non-natural. Health impact was evaluated for year 2016 (baseline) and estimated for 2020 and 2030, from annual mean concentrations reported and projected by the environmental authority. The study was carried out based on annual mean mortality rates reported for the period 2007–2016. Among the most relevant results, it was found that for 2016 the areas with the highest annual concentrations of PM2.5 were Medellín (downtown area), Caldas, and Medellín (northern area) (39.4 μg/m3, 33.7 μg/m3, and 33.2 μg/m3, respectively). Consequently, health impact estimations (mortality due to all causes in adults) showed the highest associations: 15.70% (676 cases; CI: 470.29–873.06), 12.90% (32 cases; CI: 22.04–41.34) and 12.63% (736 cases; CI: 508.65–954.76), respectively.For the Aburrá Valley Metropolitan Area in 2016, it was found that death cases attributable to PM2.5 levels were: 1971 cases (CI: 1362.96–2558.62) for adult mortality due to AC, 194 cases (CI: 92.04–284.17) due to LC and 932 cases (CI: 791.33–1063.56), figures comparatively lower than the estimates for 2030, where death cases attributable to the same pollutant were: 5867 cases (CI: 4190.12–7410.53) for adult mortality due to AC, 497 cases (CI: 265.47–666.77) due to LC and 2415 cases (CI: 2157.06–2632.99). These values were calculated from the sum of the estimations given by the BenMap model for each municipality in the Metropolitan Area. Finally, avoidable death cases were calculated for a scenario with the implementation and execution of 100% of the measures for the prevention and control of emissions from motor vehicles, as defined by the Integral Plan for Air Quality Management (PIGECA, AMVA, 2017a) for year 2030: 55.93% of infant mortality cases due to AC; 50.32% in adults due to AC; 55.73% in adults due to LC and 60.87% in adults due to IHD associated with PM2.5.