OBJECTIVES: To compare through a cost-effectiveness model Nintedanib (Vargatef®)+Docetaxel  as a second line treatment in patients with non-small cell lung cancer (NSCLC) with Docetaxel and Pemetrexed in Mexico. METHODS: We performed a cost-effectiveness analysis considering as comparators Docetaxel and Pemetrexed. An extrapolation and parameterization of the Kaplan Meier curves related to overall survival (OS) and progression free survival (PFS) (reported on the LUME-Lung1 and the meta-analysis by Popat, S., et.al., 2015) were considered in order to determine the effectiveness and incidence of adverse events for each alternative. The model was produced considering a time horizon of 5 years and an effectiveness measure of life-years gained (LYG) on OS. Because this is a therapy for an advanced disease, we only considered direct medical costs and an incremental cost-effectiveness analysis. As validation, we performed a deterministic and probabilistic sensitivity analysis. RESULTS: The average cost per patient using the Nintedanib+Docetaxel therapy was $483,670 with a 1.40 LYG; Docetaxel had a cost of $355,846 and 1.17 LYG, while, Pemetrexed had a cost of $425,361 and a 1.20 LYG. Pemetrexed vs. Docetaxel had an ICER of $2,737,254 and Nintedanib+Docetaxel vs. Docetaxel an ICER $546,580.  CONCLUSIONS: The evaluation leaves Nintedanib+Docetaxel as being a cost-effective, second-line treatment for patients with NSCLC given that it increases an average of three months on OS compared with Docetaxel (the cheapest alternative). Sensitivity analysis confirm the results obtained.