<p>Ticagrelor has been authorized for use as an antiplatelet therapy in individuals diagnosed with acute coronary syndrome (ACS). While numerous clinical trials have reported respiratory-related AEs associated with ticagrelor, real-world evidence from large populations remains limited. In this study, we aimed to assess the safety signals of respiratory, thoracic, and mediastinal disorders related to ticagrelor using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).This study utilized data from the FAERS database spanning 2011 to 2024. The reporting odds ratio (ROR) was used to quantify safety signals of respiratory, thoracic, and mediastinal adverse events associated with ticagrelor. Chi-square (χ²) or Fisher’s exact tests were used to compare serious versus non-serious cases. A prioritization scale was applied to rank the identified signals. Additionally, sensitivity analysis was conducted, using Weibull distribution to model the time-to-onset (TTO) risk of AEs.A total of 4,605 respiratory, thoracic, and mediastinal AEs associated with ticagrelor were identified, with 25 significant safety signals detected. Patient sex (<i>p</i> &lt; 0.001) and weight (<i>p</i> &lt; 0.001) were significantly associated with increased risk of serious AEs, whereas no association was observed with age (<i>p</i> = 0.287). Stratified analyses confirmed the consistent association between ticagrelor and respiratory, thoracic, and mediastinal risks. Nine signals were classified as moderate clinical priority and sixteen as weak priority. Notably, all respiratory, thoracic, and mediastinal AEs exhibited an early failure pattern. This pharmacovigilance study systematically investigated ticagrelor-associated respiratory, thoracic, and mediastinal disorders to support clinicians in optimizing cardiovascular treatment strategies.</p>