AIM: To provide a reference for high-quality and efficient manage gement of suspicious and unexpected serious adverse reaction (SUSAR) reports and to reduce the safety risks to subjects. METHODS: A total of 21 593 SUSAR reports submitted by sponsors to our hospital's drug clinical trial institution from July 2020 to June 2023 were collected. The analysis focused on the discrepancies and reasons between the sponsor's pharmacovigilance (PV) department and the investigators regarding the assessment of the causality between serious adverse events (SAEs) and the investigational drugs. RESULTS: 10 977 (50.8%) of the SUSAR reports received reported that the relevance judgment was disputed. Among those reports, the researchers considered them relevant to the investigatory drug, while the sponsor considered them irrelevant, with a total of 10 931 reports (99.6%). Among the causes of SAE given by sponsor, 4 760 (31.6%) reports were related to drug combination, 4 366 (29.0%) reports were related to prior medical history and concurrent diseases, and 4 862 (32.3%) reports were related to study disease, age, radiotherapy, surgery or surgical history, infection, own condition and chemotherapy. There were 1 077 reports (7.1 percent) for which no reason was given. CONCLUSION: In the current SUSAR reporting process, the pharmacovigilance (PV) department commissioned by the sponsor demonstrates a clear bias toward classifying serious adverse events (SAEs) as unrelated during relevance assessment. To address this issue, it is imperative to strengthen regulatory oversight of SUSAR reporting, standardize roles, responsibilities, and authority boundaries among stakeholders in the reporting process. This approach aims to ensure comprehensive coverage of SUSAR reports while enhancing accountability awareness and safety supervision capabilities across all parties involved, ultimately safeguarding the maximum protection of trial subjects' safety.