OBJECTIVE: The value of health-related quality-of-life assessments is established and inclusion in clinical decision-making is increasing. A phase III trial in second-line therapy for advanced non-small cell lung cancer (NSCLC) showed similar efficacy for pemetrexed, versus docetaxel, but key safety benefits. A study in the United Kingdom (UK) and France was conducted to determine patient value associated with individual toxicity profiles. METHODS: A discrete choice conjoint analysis was used to quantify patient preference and willingness-to-pay (WTP) for chemotherapy. Trial data plus expert opinion identified clinically meaningful toxicities that were statistically significantly different. Levels of risk of: febrile neutropenia (requiring hospitalisation) and nausea, neuropathy, alopecia, were evaluated. A sample size of 70 pre-treated NSCLC patients per country was calculated following a pilot. Patients considered unique, randomly generated sets of 10 pair-wise choice scenarios representing levels for toxicity attributes plus cost, designed to elicit trade-offs. Logistic regression analysis was applied to the stated scenario preferences against the individual attribute levels. RESULTS: Patients (N=140) were predominantly male; mean age 61 years and Stage III disease (60%). Pemetrexed was preferred to docetaxel at zero cost, with a probability of 0.81 in the UK and 0.90 in France. Overall WTP was in favour of pemetrexed, driven primarily by the risk of febrile neutropenia in the UK, odds ratio (OR) 4.4. In France, preference was driven by a reduced risk of febrile neutropenia (OR 3.2) and neuropathy (OR 3.2). Cost was not a significant determinant of choice in France; however in the UK, cost was significant determinant of choice. CONCLUSIONS: NSCLC patients prefer the enhanced toxicity profile with pemetrexed, which translates to valuable quality-of-life gains in the second-line setting. These data provide sensitive strength of preference measures and may be useful for decision-making purposes by patients, clinicians, and formulary committees.