BACKGROUND: Coronavirus disease 2019 (COVID-19) is strongly associated with an increased risk of thrombotic events, including severe outcomes such as pulmonary embolism. Elevated D-dimer levels are a critical biomarker for assessing this risk. In Gabon, early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19. This study hypothesizes that elevated D-dimer levels are linked to increased COVID-19 severity. AIM: To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions. METHODS: This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023. The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission. Data on demographics, clinical outcomes, D-dimer levels, and healthcare costs were collected. COVID-19 severity was classified as non-severe (outpatients) or severe (inpatients). A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity, with adjusted odds ratios (OR) and 95%CI. RESULTS: A total of 3004 patients were included, with a mean age of 50.17 years, and the majority were female (53.43%). Elevated D-dimer levels were found in 65.81% of patients, and 57.21% of these experienced severe COVID-19. Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19 (OR = 3.33, 95%CI: 2.84-3.92, CONCLUSION: D-dimer predicts COVID-19 severity and guides treatment, but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.