OBJECTIVES::  To carry out a cost-comparison evaluation of treating Colombian unfit patients with chronic lymphocytic leukemia (CLL) with Obinutuzumab vs. Ibrutinib from both a third-party payer and a social perspective, in the first two years of treatment. METHODS::  We carried out a deterministic cost-comparison analysis evaluating the treatment of unfit patients with CLL using Obinutuzumab vs. Ibrutinib in the first two years of treatment. We included both direct and indirect costs (lost wage for caregiver and transport) in this analysis by using a micro-costing strategy. Drug costs were obtained from the Ministry of Health Drug Price System Information and procedures costs came from SOAT-2016. Resource utilization was obtained from integrated claims records from the Ministry of Health (RIPS) and expert opinion. The base case is a 60 year old treatment-naïve and unfit patient with CLL. Indirect costs came from Ministry of Labor. Discounting for the second year was assumed at 3%. RESULTS::  The total 2-year average cost per patient for the base case receiving treatment for Obinutuzumab vs. Ibrutinib reaches 32,075 USD vs. 124,926 USD, respectively. The most important factor in the difference in annual costs are drug prices and frequency of utilization. Indirect costs for Ibrutinib are twofold those for Obinutuzumab due to the more frequent need for monitoring and evaluation considering the treatment protocol and dose. CONCLUSIONS::  Our results suggest that Obinutuzumab is a cost-saving treatment alternative over Ibrutinib in Colombia for patients with CLL in unfit patients in both direct and indirect costs. Due to the novelty of both molecules, our results are susceptible to assumptions of the model, including economic impact in the caregiver, effectiveness and safety. More research is needed to understand these economic and clinical aspects for both molecules. Future work should consider performing multi-criteria decision analyses to provide evidence to decision makers.