The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.