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Several studies have demonstrated that Mediterranean diet (MeD) has beneficial effects in the prevention of cardiovascular disease (CVD) globally but also in stroke prevention. However, there are few data of the influence of MeD in silent brain infarcts (SBI). Physical activity is also a well-known protective factor for CVD and stroke. Atrial fibrillation (AF) increases the risk of overt stroke and also SBI. We hypothesize that a healthy lifestyle would reduce the rate of SBI among AF patients. The aim of this study is to determine the association of a healthy profile (the combination of a good MeD adherence plus high level of physical activity) and the prevalence of SBI in a population with AF. To determine this association we have selected patients diagnosed of non-valvular AF (NVAF) from Seville urban area were selected from DIRAYA, the Andalusian electronic healthcare database. The inclusion criteria were: patients diagnosed of NVAF (according to International Classification of Diseases, 9th revision [ICD-9] classification) who scored 0–1 in the CHADS2 score, age ≥50 years and patients who give their consent. Patients were excluded when they had history of previous stroke/transient ischemic attack, if brain magnetic resonance imagine (MRI) was contraindicated or claustrophobia or when receiving oral anticoagulation. A total of 915 eligible patients were selected. A phone-call was made to explain the study protocol. After inclusion, patients were scheduled for a brain 3T-MRI. Baseline visit was performed at the same time and demographical data and medical history were collected. Physical activity and diet habits were also assessed by two validated self-administered questionnaires, the International Physical Activity Questionnaire (IPAQ) and the 14-item questionnaire of adherence to MeD from the Prevención con dieta mediterránea (PREDIMED) Study. All MRI scans were performed with the same 3.0 Tesla MR (Philips Ingenia CX, Release 3.1, Koninklijke, Amsterdam, the Netherlands). MRI protocol included: sagittal 1 mm 3DT1weighted gradient echo (GRE), sagittal 1,12 mm 3DT2-weighted fat sat fluid-attenuated inversion recovery (FLAIR), axial 5 mm 2DT2*-weighted GRE, and axial 3 mm 2D diffusion-weighted imaging (DWI [B0, B1000, ADC map]). SBI were defined as focal lesions with roughly the same intensity of cerebrospinal fluid. SBI were classified into acute/subacute lesions (hyperintense Mediterranean Diet and Physical Activity Protect from Silent Brain Infarcts in a Cohort of Patients with Atrial Fibrillation