PURPOSE The goal of this study was to assess the survival of patients with acquired resistance to gefitinib who underwent different subsequent treatments. METHODS From September 2007 to July 2014, a total of 103 patients with pathologically confirmed advanced non-small cell lung cancer and acquired resistance to gefitinib were retrospectively analyzed. Fifty-eight (56%) patients received chemotherapy; 36 were treated with chemotherapy and gefitinib continuation (CT + G), and 22 patients received chemotherapy (CT) alone. Twenty-two patients (22%) received continued gefitinib medication and local therapy (LT + G), and 23 (22%) received best supportive care (BSC). FINDINGS The median age of the patients was 62 years and 99 (96%) were diagnosed with adeno-carcinoma and 93 (90%) were stage IV cases. In the chemotherapy groups, patients had high objective response rates and disease control rates (CT + G, 16.7% and 42.7%; CT, 9.1% and 40.9%, respectively). The median progression-free survival times from the beginning of gefitinib resistance was 5.3 months in the CT + G group, 3.6 months in the CT group, 3.1 months in the LT + G group, and 1.4 months in the BSC group (P < 0.005). Moreover, the median overall survival time after gefitinib resistance in the CT + G group was 11.6 months, which was significantly longer than for CT (9.6 months), LT + G (8.1 months), and BSC (3.7 months) patients (P < 0.001). IMPLICATIONS Subsequent chemotherapy after acquired gefitinib resistance led to better survival rates, particularly when combined with continued gefitinib treatment. Local treatment combined with continued gefitinib is an alternative therapy when local progression has occurred. However, larger sample size studies in similar or other population groups are necessary to validate these findings.