Phase II studies have suggested that vinorelbine (V) plus gemcitabine (G) treatment has a similar response rate and better toxicity profile than cisplatin-based combination chemotherapy in non-small-cell lung cancer (NSCLC). Our aim was to evaluate whether or not the addition of cisplatin (P) to a VG regimen increases the efficacy or toxicities in chemo-naive inoperable NSCLC patients. From April 2002 to October 2003, 86 patients were enrolled. The treatment dose was V 20 mg/m2 plus G 800 mg/m2 intravenous infusion (i.v.) on days 1, 8 and 15, with/without P 60 mg/m2 i.v. on day 15, every 4 weeks. The efficacy and toxicity of the treatment were recorded. In all, 125 cycles of VG and 178 cycles of VGP were given to the patients in the VG and VGP arms, respectively (P = 0.001). The median cycle of treatment was three in the VG arm and five in the VGP arm. There were 10 partial responses (overall 23.3%) in the VG arm and 1 complete response and 19 partial responses (overall 46.5%) in the VGP arm (P = 0.022). Neutropenia, nausea, vomiting, and peripheral neuropathy were more common in the VGP arm (P = 0.023, 0.002, 0.025, 0.001, respectively). The Lung Cancer Symptom Scale showed no difference between the VG and VGP arms after two cycles of treatment or when the patient went off study. We concluded that the addition of P to VG treatment did increase both the tumor response rate and the toxicities. However, the toxicities were tolerable.