Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is effective in treating patients with non-small cell lung cancer (NSCLC) after unsuccessful chemotherapy. However, survival outcomes and predictors for its effectiveness in chemotherapy-naive NSCLC patients are still not clear. The goal of this study was to investigate the response and survival rates and identify the predictive factors for patients with advanced or metastatic disease receiving gefitinib as first-line therapy. We retrospectively analyzed the response and survival rates of patients with advanced or metastatic NSCLC who had received gefitinib as first-line therapy across six medical institutes in Southern Taiwan between May 2004 and April 2006. The relationship between the response and survival rates to the known predictive factors for gefitinib response and survival was also investigated. A total of 97 patients (65 females and 32 males) were enrolled in this study. Seventy-four patients (76%) had never smoked. Eighty-eight patients (91%) had adenocarcinoma or bronchioloalveolar cell carcinoma. The objective response rate was 56% and the disease control rate (partial response plus stable disease) was 76%. Only poor performance status (Eastern Cooperative Oncology Group score, 3-4) was statistically significantly associated with overall response in this study. The 1-year survival rate was 77%. We suggest that first-line gefitinib monotherapy is promising in some subgroups of Asian patients with NSCLC. Further randomized controlled studies are needed to validate the effectiveness of first-line gefitinib therapy.