OBJECTIVES The NHS newborn bloodspot screening programme currently screens all babies in England for five rare conditions. The objective of this study was to assess the cost-effectiveness of  expanding the screening programme to include five new rare conditions all inborn errors of the metabolism; HCU, MSUD, GA1, IVA, and LCHADD. METHODS A decision tree model was built to estimate the cost-effectiveness of the expanded newborn screening programme. Estimates of the prevalence of the five conditions and the test characteristics of screening were taken from the literature. Survival and morbidity estimates for the screened and unscreened populations were estimated from published case series. Quality adjusted life years (QALYS) were estimated from the extended EQ-5D+(C) which includes a cognitive dimension in order to capture the impact of neurological impairment and developmental delay which are known sequelae of the five conditions. Costs related to the marginal cost of the expanded screening programme, management costs of the conditions, and costs associated with the sequelae of the conditions were estimated from the pilot study of the expanded screening , case reports from the pilot, expert elicitation, published guidelines and estimates from the literature. Costs and QALYs were multiplied by survival and morbidity estimates to give lifetime estimates for the screened and unscreened populations. A probabilistic sensitivity analysis (PSA) was conducted. RESULTS The results from the deterministic analysis and PSA suggests that screening for all five conditions is cost-saving with screening associated with lower total costs and higher total QALYs compared to no screening. The incremental net benefit for all five conditions, at a threshold of £25,000 per QALY, was between £0.46 for IVA and £5.94 for GA1.  CONCLUSIONS Screening for MSUD, HCU, IVA, GA1 and LCHADD are each estimated to be potentially cost saving and result in increased quality of life compared to no screening.