BACKGROUNDYinzhihuang granule, consisting of extracts of Artemisia capillaris Thunb., Gardenia jasminoides Ellis, Lonicera japonica Thunb., and Scutellaria baicalensis Georgi is a well-known traditional Chinese patent medicine for patients with liver injury in China. However, the effects and safety of its use for pathologic jaundice in newborns require further systematic evaluation.PURPOSETo systematically evaluate the efficacy and safety of Yinzhihuang granules for the treatment of neonatal pathologic jaundice and to provide clinical evidence.METHODSChinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and VIP Database) and English databases (PubMed, EmBase, and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on Yinzhihuang granules for neonatal pathologic jaundice from the establishment of all databases to November 18, 2021. A meta-analysis was performed for selected data using STATA software. TSA software was used for trial sequential analyses of the total effective rate and adverse reactions.RESULTSA total of 19 trials and 2,221 newborns with pathologic jaundice were included in this study. Outcome measures of clinical efficacy in the experimental group were higher than in controls, including total bilirubin (WMD = -30.34, 95% CI = -35.44 to -25.23, p < 0.001), direct bilirubin (WMD = -15.03, 95% CI = -23.54 to -6.52, p < 0.001), indirect bilirubin (WMD = -11.22, 95% CI = -17.50 to -4.95, p < 0.001), recovery time (WMD = -2.96, 95% CI = -3.92 to -2.00, p < 0.001), hospitalization time (WMD = -3.83, 95% CI = -4.89 to -2.76, p < 0.001), and liver function indices. There were statistically significant differences between the two groups. Likewise, the incidence of adverse reactions, including diarrhea, erythra, and fever decreased remarkably in the trial group (RR = 0.44, 95% CI = 0.33 to 0.59, p < 0.001). Publication bias did not exist. We verified the efficacy and safety of Yinzhihuang granules with phototherapy for pathologic jaundice in newborns according using TSA analysis.CONCLUSIONYinzhihuang granules with phototherapy for neonatal pathologic jaundice are more effective than phototherapy alone. The incidence of ADRs does not increase with the application of Yinzhihuang granules. Due to the heterogeneity across the included studies, additional multicenter clinical trials with follow-ups are needed to confirm our findings.