Background:Cost effectiveness studies are essential to assess the real value of interventions with preventive or therapeutic objectives. Aim: To assess the theoretical cost-effectiveness of a vaccine against rotavirus in Chilean children of less than five years of age. Material and methods: An economic model was developed based on information on disease incidence, health care costs associated with treatment and the effectiveness and costs of vaccination. Net disease and vaccination costs were estimated from the health system perspective and were compared with life years and disability-adjusted life-years (DALYs) gained using a 3% discount rate. Local administrative and accounting hospital data and vaccine efficacy data were used to estimate healthcare costs and cost-effectiveness of vaccination. Results: A rotavirus vaccination program would prevent 10 deaths due to rotavirus gastroenteritis, 6,245 related hospitalizations and 41,962 outpatient visits during the first five years of life, per vaccinated cohort. For every 1,000 children born, the healthcare service spends US$15,077 on treatment of gastroenteritis. From the healthcare perspective, vaccination would yield a cost-effectiveness ratio of US$11,261 per DALY when the price of the vaccine is US$24 per course. Conclusions: Rotavirus vaccine can effectively reduce the disease burden and healthcare costs of rotavirus gastroenteritis and can be a cost-effective investment compared to other options