Drug-resistant tuberculosis (TB) has increased at an alarming rate in the WHO European Region. Of the 27 countries worldwide with a high burden of multidrug resistant-TB (MDR-TB), 15 are in the European Region. An estimated 78,000 new cases of MDR-TB occur annually in the Region, of which approximately 10% are extensively drug-resistant (XDR)-TB. In response, the WHO Regional Office for Europe developed a Consolidated Action Plan to Prevent and Combat Multidrug- and Extensively Drug-resistant Tuberculosis (2011–2015). Our objective was to analyse the cost-effectiveness of implementing the plan, with the expected achievements of diagnosing 85% of estimated MDR-TB cases and treating at least 75% successfully. A transmission model, using epidemiological data reported to WHO was developed to calculate expected achievements. WHO-CHOICE database was used for cost analyses. The highly cost-effective plan is expected to prevent the emergence of 250,000 new MDR-TB and 13,000 XDR-TB patients respectively, saving US$7 billion and 120,000 lives. The plan and accompanying Resolution were fully endorsed by the sixty-first session of the WHO Regional Committee for Europe in 2011. Member States need to continuously improve health system performance and address TB determinants. Research and development of new medicines, tools and patient-friendly services are also crucial.