OBJECTIVES: The high cost of chronic hepatitis C (HCV) direct-acting antivirals (DAAs) poses significant financial challenges for health payers, especially in Asia. A personalised treatment strategy based on individualised probability of SVR using oral DAAs as second line therapy would seem practical but has not been studied.   METHODS: We performed a Markov model to project health outcomes and costs for patients with genotype 1 HCV through ten treatment strategies over a life-time period. The implication of retreatment was also incorporated to reflect real-life situation. RESULTS: Using boceprevir and peginterferon/ribavirin (BOC/PR, least costly treatment) as a base case, the all-oral therapies such as ombitasvir/paritaprevir/ritonavir-dasabuvir and sofosbuvir/lediasprevir are cost-effective with ICER of USD 50,828 and USD 81641/QALY respectively, given a willingness to pay threshold of USD 52,500 (one GDP per capita in Singapore in 2015). However, the all-oral DAAs are no longer cost-effective if retreatment of interferon failures with oral DAAs were taken into account. A roadmap strategy using rapid virological response to guide use of BOC/PR and SOF/PR had the most favourable incremental cost-effective ratio (ICER, USD 27,782) relative to BOC/PR. CONCLUSIONS: The 12-week all-oral DAAs were cost-effective options using conventional drug to drug comparison. However, they cease to be cost-effective when treatment strategies incorporating DAA retreatment for interferon failures are incorporated. HCV management can be optimised by adopting individualised treatment algorithm providing a practical solution to health payers to make oral DAAs accessible to those who need them most.