Background <p>Ventilator-associated pneumonia (VAP) is a significant clinical challenge due to its morbidity, mortality, and economic burden, especially in low- and middle-income countries. This study evaluates the cost-utility of tobramycin and colistin as nebulized adjunct therapies to systemic antibiotics for managing VAP in Colombia.</p> Methods <p>A decision tree model was constructed comparing three interventions: tobramycin + systemic antibiotics, colistin + systemic antibiotics, and systemic antibiotics alone. The model used a one-year time horizon from a third-payer perspective. Clinical probabilities, costs, and utilities were sourced from literature and local databases. Sensitivity analyses (deterministic and probabilistic with 10,000 iterations) assessed uncertainty. Costs were reported in 2023 USD, adjusted by GDP deflator.</p> Results <p>Tobramycin demonstrated the highest cost-effectiveness. Incremental QALYs were 0.06 for tobramycin and 0.02 for colistin; incremental costs were US$338.09 and US$130.63, respectively. The ICER was US$5625.86 for tobramycin and US$5422.31 for colistin. At a willingness-to-pay threshold of US$5180/QALY, tobramycin had a 56.5% probability of being cost-effective.</p> Conclusion <p>Tobramycin is more cost-effective than colistin as an adjunctive nebulized treatment for ventilator-associated pneumonia (VAP) in Colombia. These findings may help inform clinical guidelines and reimbursement decisions. Further research is needed to evaluate long-term outcomes and to incorporate utility data specific to the Colombian population.</p>