The association between atrial fibrillation, stroke, and interatrial block (IAB) (P-wave duration ≥120 ms) is well recognized, particularly in the case of advanced IAB. We aimed to assess the association of IAB with mild cognitive impairment. CAMBIAD (Advanced Characterization of Cognitive Impairment in Elderly with Interatrial Block) was a case-control multicenter study, conducted in subjects aged ≥70 years in sinus rhythm without significant structural heart disease. Diagnosis of mild cognitive impairment was performed by an expert geriatrician, internist, or neurologist in the presence of changes in cognitive function (Mini Mental State Examination score 20-25) without established dementia. A total of 265 subjects were included. Mean age was 79.6 ± 6.3 years and 174 (65.7%) were women; there were 143 cases with mild cognitive impairment and 122 controls with normal cognitive function. Compared with controls, cases had longer P-wave duration (116.2 ± 13.8 ms vs. 112.5 ± 13.3 ms, p = 0.028), higher prevalence of IAB (73 [51.0%] vs. 38 [31.1%], p = 0.001), higher prevalence of advanced IAB (28 [19.6%] vs. 10 [8.2%], p = 0.002), and higher MVP ECG risk score (2.7 ± 1.4 vs. 2.2 ± 1.3, p = 0.004). IAB was independently associated with mild cognitive impairment, both for partial (odds ratio 2.0, 95% CI: 1.1 to 3.9) and advanced IAB (odds ratio 2.8, 95% CI: 1.1 to 6.7). In conclusion, in subjects aged ≥70 years without significant structural heart disease, IAB is independently associated with mild cognitive impairment. This association is stronger in the case of advanced IAB.