Since syndromic management of STDs requires treatment with at least two antibiotics per patient, one of the concerns raised by adoption of the syndromic approach is the cost of drugs, especially for developing countries with limited drug budgets. The objective of the current study is to compare the cost-effectiveness of syndromic management to current national practice for the management of STDs in Malawi. The actual cost of observed antibiotic treatment for 144 patients receiving same day treatment for two STD syndromes in Malawi was determined using prices from the Malawi government supply catalogue. This was then compared to the calculated cost of treatment had the same patients been managed syndromically according to national guidelines. The cost of drug treatment under current practice was similar to the cost of syndromic treatment. However, at least one-third of observed patients did not receive effective treatment for either likely cause of their STD syndrome and wastage accounted for 54% of total observed drug cost. Overall, syndromic management of STDs in Malawi would result in more effective treatment of STDs at no additional cost. Since the indirect costs of low treatment efficacy were not taken into account in this analysis, a net saving is likely to be realized with the adoption of syndromic management.