Objective: To analyze the cases from 280 high-risk neonates with inherited metabolic disease (IMD) in Qingdao. Methods: A total of 280 high-risk neonates screening inherited metabolic disease by serial mass spectrometry from May 2014 to September 2018 in Women’s and Children’s Hospital of Qingdao were chosen. The blood and urine were chemically analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), urine gas chromatography and genetic analysis were performed on suspected positive cases. Results: Of the 280 high-risk IMD newborns, 17 cases (6.07%) were positive by tandem mass spectrometry, including 8 cases fatty acid metabolic diseases (2.86%), 5 cases amino acid metabolic diseases (1.78%), and 4 cases organic acid metabolic diseases (1.42%), the incidence of methylmalonic acidemia was the highest, accounting for 1.42% (4/280). There were 4 cases by the final diagnosis, the total incidence rate of 1.42% (4/280); 17 cases of primary mass spectrometry positive children manifested as jaundice, hepatosplenomegaly, metabolic acidosis, abnormal muscle tone, feeding difficulties, poor reaction, convulsions or intermittent convulsions, coma, et al. Laboratory tests showed abnormal liver function, elevated blood ammonia, metabolic acidosis, fasting hypoglycemia; In the tandem mass spectrometry detection, in addition to the reduced abnormal indicators performance on avian acid carbamoyl transferase deficiency and primary carnitine deficiency, most of the indicators were significantly higher than the upper limit of the reference value. Conclusion: In the neonatal population with high risk factors in Qingdao, there is a certain incidence of IMD, and it is of great significance to perform mass spectrometry screening.