The role of nutrients in lung cancer aetiology remains controversial and has never been evaluated in the context of screening. Our aim was to investigate the role of single nutrients and nutrient patterns in the aetiology of lung cancer in heavy smokers. Asymptomatic heavy smokers (≥20 pack-years) were invited to undergo annual low-dose computed tomography. We assessed diet using a self-administered food frequency questionnaire and collected information on multivitamin supplement use. We performed principal component analysis identifying four nutrient patterns and used Cox proportional Hazards regression to assess the association between nutrients and nutrients patterns and lung cancer risk. During a mean follow-up of 5.7 years, 178 of 4,336 participants were diagnosed with lung cancer by screening. We found a significant risk reduction of lung cancer with increasing vegetable fat consumption (HR for highest vs. lowest quartile = 0.50, 95% CI = 0.31-0.80; P-trend = 0.02). Participants classified in the high "vitamins and fiber" pattern score had a significant risk reduction of lung cancer (HR = 0.57; 95% CI = 0.36-0.90, P-trend = 0.01). Among heavy smokers enrolled in a screening trial, high vegetable fat intake and adherence to the "vitamin and fiber" nutrient pattern were associated with reduced lung cancer incidence.