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BACKGROUND. Computed tomography (CT) screening is an important new tool for the early detection of lung cancer. In the current study, the authors assessed the discomfort associated with CT scanning and the subsequent wait for results and health-related quality of life (HRQoL) over time. METHODS. A total of 351 participants in the Dutch-Belgian randomized controlled trial for lung cancer screening in high-risk subjects (the NELSON trial) who had an appointment for a baseline CT scan were asked to complete questionnaires regarding their experienced discomfort and HRQoL before, 1 day after, and approximately 6 months after the CT scan. HRQoL was measured as generic HRQoL (12-item Short Form [SF-12] and EuroQol questionnaire [EQ-5D]), generic anxiety (State-Trait Anxiety Inventory [STAI-6]), and lung cancer-specific distress (Impact of Event Scale [IES]). Approximately 76.9% of the participants completed all 3 questionnaires. RESULTS. Approximately 87% to 99% of participants reported experiencing no discomfort related to the CT scan. The median SF-12, EQ-5D, STAI-6, and IES scores did not appear to change relevantly over time. Approximately 46.0% and 51.3%, respectively, of the participants reported discomfort in connection with having to wait for the results of the CT scan and dreading those results. These patients had relevantly higher STAI-6 and IES scores (P < .01) (unfavorable) at all 3 assessments. CONCLUSIONS. The current evaluation of the potential adverse effects of CT screening for lung cancer on HRQoL demonstrated no negative effects. However, waiting for the CT scan results was reported to be discomforting by approximately half of the participants. Minimizing the waiting time for the test results is therefore recommended. Cancer 2008. © 2008 American Cancer Society.