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Objective: Estimate the cost-effectiveness ratio of the directly observed treatment short course (DOTS) for treatment of tuberculosis (TB), comparing it to a variation of this treatment that includes increased home-based guardian monitoring of patients (DOTS-R)., Methods: Taking a social perspective that includes the costs for the health institutions, the patients, and their family members, and for other entities that contribute to making operation of the program effective, the costs incurred with each of the two strategies were evaluated and the cost-effectiveness ratios were estimated adopting the measures of effect used by the control programs. The estimate of the cost of each of the two strategies includes the cost to the health institutions that administer treatment, the patients and their family members, and the cost to the Ministry of Health that manages public health programs on the municipal level. Based on these costs and the number of cases cured and treatments completed as outcome measures of each of the strategies evaluated, the cost-effectiveness ratio and incremental cost were calculated., Results: The DOTS-R was found to be more cost-effective for achievement of successful treatments than the DOTS. The DOTS-R recorded costs of US$ 1 122.40 to US$ 1 152.70 for each case cured compared to values of US$ 1 137.00 to US$ 1 494.30 for the DOTS. The percentage of cases treated successfully was higher with DOTS-R than with DOTS., Conclusions: The DOTS-R is a promising cost-effective alternative for improved control of TB in endemic areas. It is recommended that the health authorities include home-based guardian monitoring of patients in their institutional management of the TB program, with the participation of health workers and the physical and financial resources that currently support this program.