Abstract Despite widespread availability of acetaminophen in Mexico, data on its pharmacokinetic properties in Mexican populations are limited. This single‐center, single‐blind, randomized, 2‐period, 2‐treatment, crossover, single‐dose‐per‐period, 2‐sequence study evaluated the bioequivalence of a test acetaminophen product available in Mexico compared with a reference 500‐mg acetaminophen product in 28 healthy adults under fasting conditions. Blood samples were collected predose and at specified intervals across a 16‐hour period following administration and were analyzed for acetaminophen using a validated reverse‐phase high‐performance liquid chromatography method. Drug products were considered to be bioequivalent if confidence intervals of natural log‐transformed C max , AUC 0‐t , and AUC 0‐∞ data were within the range of 80% to 125%. Results were inconclusive for C max due to high levels of intrasubject variability with this parameter. However, criteria for bioequivalence were met for AUC 0‐t and AUC 0‐∞ . All measured acetaminophen concentrations in this study were within a safe therapeutic range, and no adverse events were reported. The level of C max intrasubject variability observed in this study does not have any apparent clinical implications that could affect either safety or efficacy.