Objective To explore and analyze the signals of adverse drug events (ADEs) following the marketing of niraparib, providing insights for its safe clinical usage. Methods ROR, PRR, and EBGM were employed to mine and analyze adverse events reported in the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2017 to the fourth quarter of 2023. Furthermore, we validated our data at the genetic level through phenome-wide Mendelian randomization (MR) analysis. Results A total of 17 693 cases with niraparib identified as the primary suspected drug yielded 124 708 adverse event signals across 27 systemic organ categories. The top 5 systemic organ categories ranked by ROR were: various examinations ( n=22 295, 17.88%), gastrointestinal diseases ( n=20 232, 16.22%), blood and lymphatic system diseases ( n=3 182, 2.55%), various surgeries and medical procedures ( n=2 230, 1.79%), benign or malignant tumors unknown ( n=4 139, 3.32%). Preferred terms (PTs) not mentioned in the drug label included elevated carbohydrate antigen 125 (various tests), hard stools (gastrointestinal diseases), and lymphadenopathy (blood and lymphatic system diseases), and in Phenome-wide Mendelian Randomization, our findings were also validated at the genetic level. Conclusion Patients using niraparib commonly experience adverse reactions that last between 22 and 61 days, with discomfort most frequently reported in the heart, nasopharynx, and muscle areas. Therefore, prior to administering niraparib, a thorough medication assessment is recommended, particularly for female patients and those aged 55 to 79, who are more likely to have adverse reactions such as decreased platelet count, nausea, and fatigue. Healthcare professionals should fully inform patients about potential adverse reactions associated with niraparib use and develop corresponding strategies to minimize harm.