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Background: Atrial dysfunction or “cardiopathy” has been recently proposed as a mechanism in cryptogenic stroke. A prolonged PR interval may reflect impaired atrial conduction and thus may be a useful biomarker of atrial cardiopathy. We aim to compare the prevalence of PR interval prolongation in patients with cryptogenic stroke (CS) when compared to known non-cryptogenic non-cardioembolic stroke (NCNCS) subtypes.Methods: We retrospectively analyzed prospective ischemic stroke databases and included consecutive patients between December 1st, 2013 and August 31st, 2015 in three comprehensive stroke centers (Rhode Island Hospital, Hartford Hospital, and Tulane University Medical Center). Consecutive patients 18 years or older with a discharge diagnosis of ischemic non-cardioembolic stroke were included. The main outcome was ischemic stroke subtype (CS vs. NCNCS). We compared PR intervals as a continuous and categorical variable (< 200 ms; ≥ 200 ms) and other clinical and demographic factors between the two groups and used multivariate regression analyses including age and other factors deemed significant on univariate analyses to determine the association between PR interval prolongation and CS.Results: We identified 644 patients with ischemic non-cardioembolic stroke (224 CS and 420 NCNCS). The PR interval was longer in patients with CS vs NCNCS (175.4 ± 35.2 ms vs. 166.5 ± 27.7 p = 0.005). After adjusting for factors that were found to be significant in univariate analyses, a prolonged PR interval was independently associated with CS (Odds Ratio: 1.70; 95% CI 1.08-2.70; p=0.022). The association was more pronounced when excluding patients on atrio-ventricular nodal blocking agents (OR=2.64, 95% CI 1.44-4.83, p=0.002).Conclusions: A prolonged PR interval is associated with CS and may be a biomarker of atrial cardiopathy in patients with cryptogenic stroke. This association needs to be confirmed in prospective neuro-epidemiological cohorts.