Objectives To support patients in their disease management, providing information that is adjusted to patients’ knowledge and ability to process health information (ie, health literacy) is crucial. To ensure effective health communication, general practitioners (GPs) should be able to identify people with limited health literacy. To this end, (dis)agreement between patients’ health literacy and GPs’ estimations thereof was examined. Also, characteristics impacting health literacy (dis)agreement were studied. Design Cross-sectional survey of general practice patients and GPs undertaken in 2016–17. Setting Forty-one general practices in two Dutch-speaking provinces in Belgium. Participants Patients (18 years of age and older) visiting general practices. Patients were excluded when having severe impairments (physical, mental, sensory). Main outcome measures Patients’ health literacy was assessed with 16-item European Health Literacy Survey Questionnaire. GPs indicated estimations on patients’ health literacy using a simple scale (inadequate; problematic; adequate). (Dis)agreement between patients’ health literacy and GPs’ estimations thereof (GPs’ estimations being equal to/higher/lower than patients’ health literacy) was measured using Kappa statistics. The impact of patient and GP characteristics, including duration of GP–patient relationships, on this (dis)agreement was examined using generalised linear logit model. Results Health literacy of patients (n=1375) was inadequate (n=201; 14.6%), problematic (n=299; 21.7%), adequate (n=875; 63.6%). GPs overestimated the proportion patients with adequate health literacy: adequate (n=1241; 90.3%), problematic (n=130; 9.5%) and inadequate (n=4; 0.3%). Overall, GPs’ correct; over-/underestimations of health literacy occurred for, respectively, 60.9%; 34.2%; 4.9% patients, resulting in a slight agreement (κ=0.033). The likelihood for GPs to over-/underestimate patients’ health literacy increases with decreasing educational level of patients; and decreasing number of years ...