Background: The incidence of invasive pneumococcal disease (IPD) varies depending on a number of factors, including vaccine uptake, in both children and adults, the geographic location, and local serotype prevalence. There are limited data about the burden of Streptococcus pneumoniae (Spn), serotype distribution, and clinical characteristics of adults hospitalized due to IPD in Colombia. Thus, this study will attempt to bridge this gap in the literature. Methods: This was an observational, retrospective, a citywide study conducted between 2012 and 2019 in Bogotá, Colombia. We analyzed reported positive cases of IPD from 55 hospitals in a governmental pneumococcal surveillance program. Pneumococcal strains were isolated in each hospital and typified in a centralized laboratory. The objectives of this study included assessment of Spn serotype distribution, clinical characteristics, mortality, ICU admission, and the need for mechanical ventilation. Results: A total of 310 patients with IPD were included, of whom 45.5% were female. The leading cause of IPD was pneumonia (60%, 186/310), followed by meningitis. The most frequent serotypes isolated were 19A (13.87%, 43/310) and 3 (11.94%, 37/310). The overall hospital mortality rate was 30.3% (94/310). Moreover, 52.6% (163/310 patients) were admitted to the ICU, 45.5% (141/310) required invasive mechanical ventilation and 5.1% (16/310) non-invasive mechanical ventilation. Conclusion: Pneumococcal pneumonia is the most prevalent cause of IPD, with serotypes 19A and 3 being the leading cause of IPD in Colombian adults. Mortality due to IPD in adults continues to be very high.