Objective : This study aimed to identify adverse drug event (ADE) signals associated with ambrisentan, a pulmonary arterial hypertension (PAH) treatment, and guide its safe clinical use. Methods: ADE reports from the FDA Adverse Event Reporting System (FAERS) database (Q1 2007–Q2 2024) were analyzed using the Reporting Odds Ratio (ROR) method. Data were standardized using MedDRA version 26.0. Results: Among 45,007 ADE reports, 74.26% involved females aged 18–65, with 85.75% from the U.S. Common outcomes included hospitalization (46.19%). A total of 267 positive ADE signals were detected, including hematotoxicity (e.g., decreased serum iron) and nervous system-related events (e.g., exertional dizziness), not listed in the drug insert. Time-to-onset analysis showed most ADEs occurred within 0–30 days (9.05%) or after 360 days (10.01%) of treatment. Conclusion: This study confirmed known ambrisentan ADEs (e.g., peripheral edema, headache) and identified new signals (e.g., atrial flutter, syncope, jaw pain). Comprehensive monitoring is essential to ensure patient safety and optimize treatment outcomes.