OBJECTIVES: Malaysia is experiencing an escalation of dengue epidemic activity. The candidate vaccine currently at the most advanced stage of development has demonstrated its efficacy in two large scale efficacy studies. This study aims to estimate the potential health and economic impact of the vaccine in Malaysia under different vaccination strategies. METHODS: A dengue dynamic transmission mathematical model was employed to evaluate the impact of dengue vaccination program on the incidence, mortality and economic burden of the disease. The model was calibrated and validated with Malaysia specific epidemiological data and vaccine efficacy data from phase-III efficacy studies. The impact was evaluated over a 10-year period from provider perspective. Two vaccination strategies, targeted-hotspots (THS, covered population in 6 selected hotspot districts) and nationwide (NW, covered the whole Malaysian population), were simulated. Both strategies comprised of routinely vaccinated children aged 13 and a catch-up cohort from ages 14 to 30 who were vaccinated over a 1 year duration. Probabilistic and univariate sensitivity analyses on key parameters were conducted to examine uncertainty in the model. All costs were expressed in 2013 USD. RESULTS: The cost per dengue case from provider perspective was USD999.02. The model predicted that dengue vaccination under the THS strategy would prevent 448,124 [95%CI: 292,875; 632,375] dengue cases, 509 [95%CI: 335; 707] dengue-related deaths, 11,785 [95%CI: 7,888; 16,329] life years lost and 16,751 [95%CI: 11,128; 23,281] DALYs. Nationwide vaccination would prevent 1,060,222 [95%CI: 694,181; 1,490,929] dengue cases, 1,202 [95%CI: 797; 1,672] dengue-related deaths, 27,834 [95%CI: 18,756; 38,501] life years lost and 39,584 [95%CI: 26,464; 54,968] DALYs. The total dengue treatment cost saved for THS and NW vaccination strategy were USD163,859,846 [95%CI: 109,093,124; 235,805,776] and USD386,962,641 [95%CI: 257,410,189; 557,347,377] respectively. CONCLUSIONS: We conclude that dengue vaccination would significantly reduce the disease and economic burden in Malaysia, especially if it is introduced during current dengue epidemic.