Nucleoside analogue-induced lactic acidosis is an often fatal condition in patients with HIV. There is only one report of successful treatment with riboflavin. We describe a 30-year-old female with AIDS and nucleoside analogue-induced lactic acidosis that exacerbated shortly after introducing total parenteral nutrition and reversed within hours after the addition of thiamine. Successful treatment of nucleoside analogue-induced lactic acidosis with a high dose of thiamine supports the hypothesis that vitamin deficiency is an important cofactor in the development of this rare and unpredictable condition in patients with HIV. We suggest that high dose B-vitamins should be given to any patient presenting with lactic acidosis under nucleoside analogue treatment.