Weekly docetaxel seems to be safe and effective compared with traditional tri-weekly docetaxel as a second-line treatment for non-small cell lung cancer. However, the risk factors for severe toxicity of weekly docetaxel in this group of patients are not well-described. Patients with advanced non-small cell lung cancer receiving weekly docetaxel as second- or third-line treatment at a medical center between 1999 and 2003 were identified from cancer registry and pharmacy records. The clinical characteristics, prior chemotherapy regimens, docetaxel administration schedules, and treatment efficacy were collected. Logistic regression was performed to identify risk factors for adverse outcomes and Cox's proportional hazards model was used to analyze cumulative-dose related adverse events. A total of 155 patients were analyzed for treatment effect and toxicity. The overall response rate of weekly docetaxel was 5.2% and the median survival was 8.1 months. The incidence of treatment withdrawal due to adverse events was 43.2% and was significantly related to previous anthracycline use (odds ratio, 4.582; p=0.0144) and chronic hepatitis B or C virus infection (odds ratio, 3.928; p=0.0058). The incidence of grade 3 or 4 neutropenia was 23.2% and was significantly associated with old age (odds ratio, 7.232; p<0.001), lower baseline white blood cell counts (odds ratio, 5.57; p<0.05), and chronic hepatitis B or C virus infection (odds ratio, 3.25; p<0.05). The incidence of fluid retention was 41.3% and the median cumulative dose of docetaxel at onset was 327 mg/m(2). Abnormal liver function status significantly increased the risk for fluid retention (odds ratio, 2.368; p<0.05); while pre-medication with steroids (odds ratio, 0.184; p<0.01), elevated albumin (odds ratio, 0.237; p<0.01), and previous surgical resection (odds ratio, 0.341; p<0.05) decreased the risk. Weekly docetaxel given as second- or third-line chemotherapy to patients with advanced non-small cell lung cancer harbors significant side effects. It should be given cautiously in elderly patients and in patients with chronic viral hepatitis or low white blood cell counts.