Background: This paper describes the performance of the Tuberculosis (TB) control programme in the Eastern Cape Province. The aim of the study was to evaluate the tuberculosis treatment outcomes as well as to identify factors that contribute to treatment failures in health districts of the Eastern Cape Province from 2003 to 2005. TB can only be controlled and eventually eliminated in the context of a National Tuberculosis Control Program (NTCP). Such a program must operate within the general health service of each country. Although considerable progress has been made with TB control efforts in South Africa since 2000, there is still little sign that the epidemic is abating in the Eastern Cape Province. Method: The study was a descriptive study and the methodology employed in this evaluative study took cognizance of the main approaches used globally (World Health Organization and the International Union Against Tuberculosis and Lung Disease) to assess the performance and quality of Tuberculosis Control Programs. 152 336 records from the Electronic TB Register for the period 2003 – 2005 were systematically reviewed and a random sample design of 252 primary health care facilities with probability proportional to size was used to collect information on health system related factors that contribute to treatment failures with emphasis to input, process and output indicators for the TB Control programme including proper implementation of DOTS strategy. Results: Overall TB treatment outcomes in Eastern Cape Province did not reach the national targets for the period 2003 – 2005. A cure rate of 39.7% for new smear positive patients in 2005 was reported. Only Chris Hani district reached a national target of 70% for smear conversion rate in 2005. The successful treatment outcomes were below 85% threshold suggested by the World Health Organization. Cure rates never reached 50% for the three-year study period. Defaulting from treatment remained a challenge for the TB control programme in the Eastern Cape Province. There has been an increasing number of patients with treatment outcome not evaluated in 2005 from 20.1% to 24.7% in new smear positive cases and in re-treatment smear positive cases, this increased from 21.2% to 27.3%. Conclusion: The findings of the study reveal that, despite considerable efforts made by the NTCP, little change was noted in treatment outcomes. Efforts to provide effective TB treatment using DOTS at district and facility level in the province are constrained by failure of most districts to reach a 100% DOTS coverage. Patients are accurately diagnosed, recorded into the register, drug supply is regular and uninterrupted but there has been a slow increase in the proportion of patients cured and there are an increase number of defaulter rates and patients with treatment outcomes which are not evaluated. An improved base of information is needed to assess the TB morbidity impact more accurately. Human resources were among the most important resources, which were found lacking and health system managers have the responsibility and challenge of ensuring that maximum benefit is derived from these to maintain and expand health services.