Neonatal screening aims to detect asymptomatic infants at early stages to prevent the occurrence of body dysfunction and irreversible damage, so as to reduce the rate of infant disability and mortality. Mass spectrometry makes possible the simultaneous measurement of several metabolites and, consequently, the detection of several diseases in one blood spot and in a unique analysis. This study assessed the outcome and cost-effectiveness of neonatal screening using tandem-mass spectrometry (MS/MS). Patients who underwent MS/MS screening for inherited metabolic diseases (IMD) from 2009Q1-2018Q4 were identified with another MS/MS screening plus specified tests and confirmed by gene sequence analysis. All records were extracted from a screening management system in Neonatal Screening Center of Zhejiang province. Direct costs were estimated from the perspective of the Chinese healthcare system. Of the 3,040,815 neonates screened, 26,297(0.86%) neonates were suspected positive after first-round screening and called back to take another MS/MS screening. 25,670(97.62%) of them followed the latter procedures and finally 574(2.24%) cases were diagnosed through gene sequence analysis . The most frequent cause of IMD is fatty acid oxidation disorders (n=248), in most cases organic acidemias (n=211), followed by amino acid diseases(n=115). The costs of MS/MS was RMB$175 for screening and RMB$390 for follow-up, RMB$60 or 116 for specified tests, RMB$3120 for gene sequence analysis and RMB$80 for genetic counselling. The medication expenditures for detection of one single IMD patient was RMB$952,405.04. Overall the cost is huge. Neonatal screening for IMD using MS/MS in common neonates may not be cost-effective, this needs to be confirmed using data on observed mortality and disability reduction.The results prompt the need of prudent consideration for nationwide promotion of IMD neonatal screening using MS/MS.