We conducted a retrospective study to identify prognostic factors in the lactic acidosis syndrome (LAS) caused by nucleoside reverse transcriptase inhibitors (NRTIs) in patients with HIV/AIDS. Fifty-eight cases of LAS were included in our analysis, 8 from our hospital spanning the years 1992-2002, and 50 reported in the English language literature from 1986 through 2002. Peak venous lactate level was the best predictorof mortality. Zidovudine was associated with higher lactate levels and higher mortality than stavudine and lamuvidine. Mortality declined progressively after 1986 when the first cases of NRTI-related LAS were described. Increased mortality with zidovudine in this study appears due in part to its greater use prior to 1990 when LAS was not widely recognized as a potential complication of NRTI therapy.