ObjectiveThe alpha rhythm has been a subject of research for the past few decades. Right-left alpha amplitude asymmetry is a common phenomenon. Several explanations have been proposed to explain this asymmetry, including differences in skull thickness. Our research aims to improve our understanding of the relationship between alpha asymmetry and skull thickness as measured by CT/MRI images. MethodsWe analyzed EEGs to study alpha rhythm characteristics. Alpha rhythm amplitude was measured using peak-to-peak values in O1 and O2 reference channels. Significant alpha asymmetry was defined as exceeding 20%. Skull thickness differences at corresponding locations were determined through CT/MRI scans. We examined the correlation between alpha and skull thickness asymmetry using Kruskal-Wallis, Spearman correlation, and median regression. ResultsWe examined 401 EEGs and images, categorizing patients into three groups based on alpha asymmetry. Group 1(n= 211) had less than 20 percent alpha asymmetry, Group 2(n=107) showed higher right-side alpha amplitudes, and Group 3(n= 83) displayed higher left-side alpha amplitudes. Our analysis revealed a significant association between groups with asymmetry and skull thickness differences (p<0.001), with a Spearman correlation (Rs) of −0.25 (p<0.001), indicating a significant negative correlation. After adjusting for age, sex, and handedness, Median Regression confirmed a statistically significant variation in skull thickness difference among the groups. SignificanceThe present study involving a large cohort, the first of its kind, demonstrated a significant relationship between alpha amplitude asymmetry and skull thickness.