<p>This study aimed to retrospectively evaluate the association between periradicular lesions in maxillary premolar and molar roots and pathological changes in the maxillary sinus using cone-beam computed tomography (CBCT). CBCT scans including the maxillary posterior region were retrospectively analyzed. A total of 300 patients and 540 maxillary premolar and molar roots with periradicular lesions meeting the inclusion criteria were included. The presence of periradicular lesions and the proximity of the affected roots to the maxillary sinus were evaluated. Maxillary sinus pathologies were classified as mucosal thickening (MT) or odontogenic maxillary sinusitis (OMS). Associations between categorical variables were analyzed using Fisher’s exact test with Monte Carlo correction and the Pearson chi-square test. Multiple comparisons were performed using the Bonferroni-corrected Z-test. Statistical significance was set at <i>p</i> &lt; 0.05. A significant association was found between tooth root type, including premolar and molar root subtypes, and the presence of MT and OMS (<i>p</i> &lt; 0.001). The palatal root of the maxillary first molar showed the strongest association with maxillary sinus involvement, whereas premolar roots showed a weaker association than molars. In male patients, MT associated with single-rooted maxillary first premolars (<i>p</i> = 0.044) and OMS associated with the palatal root of the maxillary first molar (<i>p</i> = 0.003) were more frequent than in female patients. The palatal root of the maxillary first molar was the root type most strongly associated with both MT and OMS. Although premolars showed a weaker association with sinus pathology than molars, their potential role in OMS should not be overlooked.</p>