Objective: We compared the COBAS® acetaminophen and salicylate assays (Roche Diagnostics) with the Stanbio GDS assays (Stanbio Laboratories) that are currently used in our laboratory with respect to interferences from hemolysis and lipemia. Methods: Acetaminophen and salicylate were added into human serum with varying concentrations of hemoglobin or Intralipid® to generate a range of acetaminophen and salicylate concentrations. Then the COBAS® and GDS assays were used to measure the apparent drug concentrations; the H and L indices were measured to determine the extent of hemolysis and lipemia present in each specimen. Results: Both hemolysis and lipemia have less effect on the COBAS® acetaminophen and salicylate assays than on the GDS assays. Conclusions: The COBAS® assays for acetaminophen and salicylate are preferable to the current GDS assays in clinical toxicology laboratories.