Background: Population health diagnoses are a fundamental tool to guide health policies and programs, and consequently, public health requirements. In this perspective, the burden of disease in inhabitants of Colombian Orinoquia is quantified for the first time. Methods: A descriptive population-based study that was based on secondary sources was carried out, which aimed at measuring the burden of the disease in the Colombian region of Orinoquia, using the simplified synthetic indicator of disability-adjusted life years (DALYs) of the global health estimation methodology. We used mortality records from the National Administrative Department of Statistics (DANE) and service provision records from the Ministry of Health and Social Protection of Colombia, both records from the year 2017, available on the Integrated Social Protection Information System. Results: 288,740.2 DALYs occurred (95% UI 210,714.6-382,948.8), with higher reports for men (59%); group of non-communicable diseases accounted for 62.3% of DALY (179,993.6, 95% UI, 115,030.2-268,405.0), followed by external cause injuries group which contributed 24.6% (71,000.0, 95% UI, 25,638.1-134,013.1), and group of communicable, maternal, neonatal, and nutritional disorders which contributed 13.1% (37,746.0, 95% UI, 28,048.0-50,239.7). Interpersonal violence was the primary cause specific of DALYs with 9.8% of the burden, (28,290.0, 95% UI, 7,365.1-64,208.1). Conclusions: Most DALYs in Orinoquia are produced by non-communicable diseases (NCD), largely caused by neoplasms and cardiovascular disease, which increased with age. However, when considered by specific cause of illness or injury, interpersonal violence is indicated as the main cause of DALYs, affecting mainly young men, possibly as an expression of social inequality, substance use, criminality, and insecurity. It is important to highlight that this region has been recognized as an area of armed conflict, drug trafficking, and poverty.