Objectives: Based on previous studies, analyze risk factors (age and combination) contributing to the severity of Xiyanping Injection’s (XYP) adverse events (AEs) by a novel method. Methods: Total AEs linked to the use of XYP injection were classified as general or serious and analyzed in the China National Adverse Drug Reaction Monitoring Information System (2004-2020). Data were analyzed with respect to age and herb-drug combination (ribavirin, ceftriaxone, penicillin sodium, ambroxol hydrochloride, clindamycin, cefoxitin sodium, azithromycin, ceftazidime, amoxicillin sodium and clavulanate potassium, levofloxacin hydrochloride, cefazolin sodium pentahydrate and cefuroxime) by variable importance for projection (VIP). Results: 28599 AEs (general27037, severe 1562) relating to XYP’s combination were included. Based on the VIP value and correlation coefficient, the results showed that in 0-6 years old, XYP -ribavirin, -ceftazidime and -ambroxol hydrochloride combination indicate positive impact on the severity of AEs. In 7-17 years old, XYP-cefoxitin sodium and -azithromycin combination tended to have general AEs. XYP-cefazolin sodium pentahydrate and -amoxicillin sodium and clavulanate potassium combination tended to have severe AEs. In 18-40 years old, XYP-cefoxitin sodium combination tended to have general AEs. Under the influence of XYP- ribavirin and -clindamycin combination, it tended to have severe AEs. In 41-65 years old, Under the influence of XYP-cefatriaxone, -penicillin sodium and -cefoxitin sodium combination, it tended to have severe AEs. In>65 years old, XYP-RB, clindamycin and -amoxicillin sodium and clavulanate potassium combination tended to have general AEs. Under the influence of XYP-cefoxitin sodium and -ceftazidime combination, it tended to increase the severity of AEs. The two groups had the same impact on the severity of AEs. Conclusions: VIP scores are useful in evaluating the risk factors affecting outcome indicators in clinical studies. It is recommended that clinical practitioners should pay attention to the metabolic characteristics of different age groups and strictly implement standardized operations such as medication interval and flushing.