Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods. We retrospectively reviewed an institutional database to identify patients with advanced EGFR mutation with acquired resistance who subsequently received chemotherapy. Patients were classified as receiving chemotherapy with continued erlotinib or chemotherapy alone. We assessed differences in outcomes between the two strategies. Results. Seventy-eight patients were included, 34 treated with chemotherapy and erlotinib and 44 treated with chemotherapy alone. Objective response rate was evaluable in 57 patients and was 41% for those treated with chemotherapy and erlotinib and 18% for those treated with chemotherapy alone. After adjusting for chemotherapy regimen and length of initial TKI course, the odds ratio for the response rate was 0.20 (95% confidence interval: 0.05-0.78; p = .02) favoring treatment with chemotherapy and erlotinib. The median progression-free survival was 4.4 months on chemotherapy and erlotinib and 4.2 months on chemotherapy alone (adjusted hazard ratio = 0.79; 95% confidence interval: 0.48-1.29; p = .34). There was no difference in overall survival. Conclusion. This is the first study, to our knowledge, to demonstrate that continuation of EGFR TKI with chemotherapy in patients with acquired resistance improves outcomes compared with chemotherapy alone. We observed an improved response rate but no difference in progression-free survival or overall survival. A larger prospective clinical trial is needed to evaluate this promising strategy further.