OBJECTIVES: To perform a cost-effectiveness evaluation, from the provider perspective, of Erlotinib in the treatment of NSCLC patients, who had failed to previous chemotherapy compared to Docetaxel and Pemetrexed. METHODS: A literature review about the efficacy of Docetaxel, Pemetrexed and Erlotinib on the NSCLC treatment with previous failure to chemotherapy was done. Direct medical costs were expressed as 21 day cycles, it included toxicity cost (fever, neutropenia, rash and diarrhea). The economic evaluation was performed calculating the cost of clinical success (CS). This cost was defined as the required number of patients treated (RPT) in order to achieve 1 progression free patient (PFP) or dead during the following 6 months after the start of the treatment. RESULTS: The cost for 6 months follow-up was USD$730.59 for Erlotinib, USD$7976.20 for Docetaxel and USD$8031.09 for Pemetrexed. The RPT for Erlotinib was lower than the RPT for Docetaxel and Pemetrexed, (6.69, 9.13 y 8.42 patients respectively).  The cost for achieving a CS was USD$51,073.53, USD$72,853.27 and USD$67,596.08 respectively. The lower RPT to maintain one PFP at 6 months with Erlotinib represents an institutional saving of USD$21,779.74 vs. Docetaxel and USD$16,522.55 vs. Pemetrexed. CONCLUSIONS: Erlotinib is a more effective alternative in achieving a longer progression-free survival than Docetaxel and Pemetrexed in the Mexican context. The best hematologic safety profile of Erlotinib (lack of fever or neutropenia) offers an additional cost reduction by less toxicity of the treatment. The cost-effectiveness analysis shows that the use of Erlotinib is a dominant therapy, since it consumes fewer resources to obtain a CS. This savingss might enhance the public health expenditure between 24% (vs Pemetrexed) – 30% (vs Docetaxel).