This current investigation was aimed to generate signals for adverse drug events of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All adverse event (AE) reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio(PRR), Bayesian confidence propagation neural network(BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10756 AE reports were identified commonly observed in cardiovascular, endocrine, musculoskeletal, gastrointestinal, hepatobiliary, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be associated with multiple adverse pregnancy conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.