Groundwater is the primary source of water for people living in rural areas, especially during seasons when surface water is contaminated or unavailable. In Colombia, people use groundwater as drinking water without additional treatment. In addition, there is no infrastructure for wastewater collection and sewage treatment in the region of the Middle Magdalena Valley. The current study aims to evaluate the quality of groundwater in this region to determine any potential health hazards associated with its consumption. To reach the objective, three (3) physicochemical and microbiological sampling campaigns were carried out during different hydrological periods. A total of 428 groundwater samples were analyzed for over 28 parameters. The results were compared with the water quality standards proposed by the US EPA and Colombian regulations for human consumption. The analysis revealed the presence of total and fecal coliforms in 89% and 58% of the analyzed samples, respectively, identifying them as the main contaminants in groundwater. Furthermore, the pH levels did not meet the standards set by the US EPA in 33.8% of the cases and by Colombian regulations in 31.02%. Additionally, 32.8%, 17.6%, 14.3%, and 10.9% of the samples failed to meet the established thresholds for apparent color, magnesium, iron, and nitrates, respectively, under both standards. Moreover, only the analyses of selenium, mercury, and zinc complied with the quality standards under both regulatory frameworks. Based on the Colombian Drinking-Water Quality Risk Index (CDWQRI-IRCA), the risk associated with water quality meant for human consumption was assessed. The results showed that over 84% of the samples analyzed posed a high risk to human health, 4.6% posed a medium risk, 5.5% posed a low risk, and only 5.7% posed no risk at all. Additionally, official mortality statistics for children under four years old were reviewed, which revealed two deaths in 2019 due to Acute Diarrheal Disease (ADD) caused by consumption of contaminated water. Therefore, it is crucial to implement water treatment systems, establish aqueducts in rural areas, and conduct rigorous and systematic monitoring of drinking water to ensure it is safe for human consumption. It is also important to track morbidity and mortality rates associated with water consumption.