Background Globally, 16 billion injections are administered each year of which 95% are for curative care. India contributes 25-30% of the global injection load. Over 63% of these injections are reportedly unsafe or deemed unnecessary. Objectives To assess the incremental cost per quality-adjusted life-year (QALY) gained with the introduction of safetyengineered syringes (SES) as compared to disposable syringes for therapeutic care in India. Methods A decision tree was used to compute the volume of needle-stick injuries (NSIs) and reuse episodes among healthcare professionals and the patient population. Subsequently, three separate Markov models were used to compute lifetime costs and QALYs for individuals infected with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Three SES were evaluated-reuse prevention syringe (RUP), sharp injury prevention (SIP) syringe, and syringes with features of both RUP and SIP. A lifetime study horizon starting from a base year of 2017 was considered appropriate to cover all costs and consequences comprehensively. A systematic review was undertaken to assess the SES effects in terms of reduction in NSIs and reuse episodes. These were then modelled in terms of reduction in transmission of blood-borne infections, life-years and QALYs gained. Future costs and consequences were discounted at the rate of 3%. Incremental cost per QALY gained was computed to assess the cost-effectiveness. A probabilistic sensitivity analysis was undertaken to account for parameter uncertainties. Results The introduction of RUP, SIP and RUP + SIP syringes in India is estimated to incur an incremental cost of Indian