Background The present study aimed to comprehensively investigate the occurrence and risk factors of adverse events (AEs) or adverse drug reactions (ADRs) (especially for thrombocytopenia and bleeding) in Chinese female patients receiving bivalirudin during percutaneous coronary intervention (PCI). Methods A total of 918 female patients from 27 Chinese medical centers took bivalirudin as anticoagulant for PCI were enrolled in this prospective, multi-center, intensive monitoring study. Safety data (AEs, ADRs, thrombocytopenia and bleeding) were collected from admission to 72 h post bivalirudin administration; then, patients were followed up at the 30th day with the safety data collected as well. Results One hundred and twenty (13.1%) patients occurred AEs, among which 7 (0.8%) cases experienced severe AEs, and 2 (0.2%) cases died. Besides, 40 (4.4%) patients occurred bivalirudin-related ADRs, in which 3 (0.3%) cases experienced severe ADRs, but 0 (0.0%) cases died. It was of note that 27 (2.9%) and 13 (1.4%) patients experienced thrombocytopenia and bleeding, respectively. Subsequent multivariate analyses observed that: clinical presentation of spontaneous coronary artery dissection (SCAD) (odds ratio (OR) = 3.191, P = 0.004), CRUSADE high risk (OR = 2.075, P = 0.031), multiple culprit vessel (OR = 2.328, P = 0.019) independently correlated with higher risk of bivalirudin-related ADRs; clinical presentation of SCAD (OR = 4.388, P = 0.002) and multiple culprit vessel (OR = 2.974, P = 0.010) independently linked with raised thrombocytopenia risk; history of diabetes mellitus (OR = 5.227, P = 0.007) and CRUSADE high risk (OR = 4.475, P = 0.016) were independent factor related to elevated bleeding risk. Conclusion Bivalirudin is well tolerated with low ADRs, thrombocytopenia and bleeding incidences in Chinese female patients undergoing PCI.