Many diet quality scores exist, but fully food-based scores based on contemporary evidence are scarce. Our aim was to develop a food-based diet score based on international literature and examine its discriminative capacity and socio-demographic determinants. Between 2006 and 2013, dietary intake of 129,369 participants of the Lifelines Cohort (42% male, 45 ± 13 years (range 18–93)) was assessed with a 110-item food frequency questionnaire. Based on the 2015 Dutch Dietary Guidelines and underlying literature, nine food groups with positive (vegetables, fruit, whole grain products, legumes&nuts, fish, oils&soft margarines, unsweetened dairy, coffee and tea) and three food groups with negative health effects (red&processed meat, butter&hard margarines and sugar-sweetened beverages) were identified. Per food group, the intake in grams per 1000 kcal was categorized into quintiles, awarded 0 to 4 points (negative groups scored inversely) and summed. Food groups with neutral, unknown or inconclusive evidence are described but not included. The Lifelines Diet Score (LLDS) discriminated well between high and low consumers of included food groups. This is illustrated by e.g. a 2-fold higher vegetable intake in the highest, compared to the lowest LLDS quintile. Differences were 5.5-fold for fruit, 3.5-fold for fish, 3-fold for dairy and 8-fold for sugar-sweetened beverages. The LLDS was higher in females and positively associated with age and educational level. The LLDS is based on the latest international evidence for diet-disease relations at the food group level and has high capacity to discriminate people with widely different intakes. Together with the population-based quintile approach, this makes the LLDS a flexible, widely applicable tool for diet quality assessment.