Background: Cryptogenic stroke (CS) represents 25% of ischemic strokes. Especially after CS, the detection of atrial fibrillation (AF) is important because it provides clues to the mechanism of stroke. However, the relationship between AF and stroke appears more complex than a simple cause-effect mechanism, suggesting that the association between AF and stroke may be due to other systemic and atrial factors including systemic inflammation that may lead to atrial remodeling and subsequent atrial cardiopathy.Objective: The aim of this study was to evaluate the relationship among different electrocardiographic parameters, inflammatory markers and in-hospital AF occurrence after acute CS. Methods: 222 patients with CS underwent 12-lead resting ECG at admission and 7-day in-hospital ECG monitoring. The following indices were evaluated: P-wave dispersion (PWD), P-wave index, P-wave axis, atrial size and high-sensitivity-C reactive protein (CRP). Results: AF was detected in 44 patients. AF-group had significantly higher PWD, P-wave index, PR interval, CRP and greater frequency of abnormal P-wave axis in comparison with no-AF group. There was a significant correlation between CRP and PWD (r=0.28). By using the mediation analysis, performed according to the “bootstrapping” method, we found that PWD is a significant mediator variable of the relationship between CRP and AF occurrence, accounting for 40% of the association. Conclusions: In cryptogenic stroke, high PWD is partly due to systemic inflammation that increases AF risk possibly via atrial electric remodeling. These findings could also suggest inflammation as a possible therapeutic target in order to prevent atrial electrical alterations and finally AF occurrence in CS.