Purpose: The objective of this study is to develop a method based on Markov models for calculating the prevalence of stroke taking into account new incident cases and to apply the methodology to the assessment of the prevalence-based cost-effectiveness of thrombolytic treatment. Methods: A Markov model is used to reproduce the natural history of stroke beginning with the general population. The first step in the study was to run the model in order to build the survival matrix from the initial population vector. The second step was to ascertain the number of individuals in the origin of each annual cohort. The validation of the method was achieved by comparison with Auckland estimates and the use of the Dismod II programme. Prevalence figures were used to calculate the cost-effectiveness of thrombolysis for stroke in 2000 and 2010. Results: Stroke prevalence rates per 100,000 for the whole population are 898 for men, 686 for women and 774 combined. Rates for stroke-related disability are 358 for men, 275 for women and 309 combined. If 10% of stroke patients had been received thrombolytic treatment in previous years, in the year 2000 the number of disabled would have been reduced by 150 and would have won 50.21 QALYs. The impact on costs would have been that Basque Society (2,100,000 inhabitants) would have spent 1,223,345 € in the intervention and would have saved 1,553,100 € by avoided care. Given the foreseeable ageing of the population, those figures will rise importantly in 2010 because the number of disabled avoided would be 298. Conclusions: This study provides for the first time a method that allows the calculation of the population prevalence of the states that constitute Markov models. In this sense, it opens a window to prevalence-based economic evaluations. The calculation of prevalence is easily followed by the assessment of the efficiency of the intervention and the budget impact. The application to the example of the thrombolysis shows that it is a dominant intervention because saves costs and produces a net benefit in health. The advantage of this approach is that decision-makers can take into account the impact of its introduction in the Basque Country.