OBJECTIVES: The annual reported incidence of varicella in Mexico between 2010-2014 ranged from 221,000-371,000 cases annually. Seroprevalence data indicates that the true number of cases is likely between 1.6-2.3 M annually. Despite availability of varicella vaccines in the private sector and for selected patients in the public sector since 2000, vaccine uptake remains variable. The objective of this study was to evaluate the cost-effectiveness of possible varicella vaccination strategies in Mexico. METHODS: A dynamic transmission model of varicella infection was calibrated to reported age-specific outpatient varicella incidence data from 2003-2011, and adjusted for care-seeking behaviour patterns. Ten experts from Mexican health institutions provided input to summarize patterns of health care resource utilization (HCRU) for natural varicella among patients in different age groups (<1, 1-4, 5-9, 10-14, 15-44, 45-64, 65+). This was combined with local unit cost data to estimate varicella treatment costs. Five vaccination strategies were considered (1 dose; 1 dose + catchup 2^nddose; 1 dose + campaign; 2 dose; and 2 dose + campaign). RESULTS: All strategies were cost-saving and will vary between 3.17T MXN to 3.5T MXN over 10 years (145B to 162B USD). The 1 dose strategy will reduce varicella cases and deaths by 35% in Year 1, 80% in Year 5, and 90% in Year 3. Higher-order strategies such as 2 dose + campaign will reduce varicella burden more quickly, lead to reductions of 61% , 87% and 92% in years 1,5, and 10. CONCLUSIONS: Both one and two dose universal varicella vaccination are cost-saving interventions, due to high use of health care resources for management of varicella in Mexico. Conservative rates of coverage (90% 1^st dose and catchup, 80% 2^nd dose) were assumed so health benefits could actually be higher. Choosing a vaccination strategy will depend on goals for speed of reduction of disease burden and budget concerns.