OBJECTIVES During 2007 (first semester), 21 rubella cases were confirmed in Fortaleza, Brazil. Immediately after notifying the cases, an intensive vaccination program was conducted to contain disease spread. Low compliance to vaccination campaigns by the Ministry of Health along with State and Municipal Health Departments is possibly related to observed rubella cases. The objective of this research was to evaluate the long-term cost-effectiveness of an intensive rubella vaccination program in Fortaleza, Brazil. METHODS A four-state Markov model was created to follow two hypothetical population cohorts, one with current vaccination characteristics (i.e., do-nothing strategy) and another following an intensive vaccination program. Target population was men (1-39 years) and women (1-49 years) residing in Fortaleza in 2007 (1,009,270 inhabitants). The two cohorts were compared against costs and cumulative number of rubella cases over time. Transition probabilities were taken from a pre-post vaccination study of militaries in Fortaleza where rubella cases were found (N=600). The societal perspective and a 5-year time-horizon were used. Costs included were: vaccines, rubella management (physician, ER visits, drugs, laboratory tests and absenteeism), vaccine adverse reactions, and labor. Costs were reported in 2009 Reais (1BRZ=0.42USD). Univariate sensitivity analysis evaluated variations in input parameters. RESULTS Following 5 years, the intensive vaccination program resulted in 24.6 cases per 100,000 inhabitants, and the do-nothing strategy 79.7 cases. The resultant cost per 100,000 inhabitants of the two comparators were R$42,916 and R$43,405 for the intense vaccination program and the do-nothing strategies, respectively. The vaccination intervention was dominant over do-nothing in an incremental analysis. Parameters sensitive to variations were vaccine cost, immunization rate, and growth rate of rubella cases. CONCLUSIONS The present study suggests that improving compliance rates to vaccination programs is considered a cost-effective alternative to prevent future illnesses, even in the case of rubella, a self-limited disease with mild-to-moderate symptoms and complications.