One of the major enzymes of the cytochrome P450 drug-metabolizing system, CYP2D6, shows a high degree of genetic polymorphism and variability in activity. Based on the degree of CYP2D6 activity, individuals can be broadly classified as poor metabolizers (PMs) or extensive metabolizers (EMs); the metabolism of CYP2D6 substrates differs among PMs and EMs. The metabolism of various drugs that are substrates of CYP2D6 has been used as a marker for metabolic phenotype, calculating the plasma or urinary metabolic ratio of the parent compound to its metabolite. The current analysis evaluates the use of the O-desmethylvenlafaxine-venlafaxine ratio (ODV/VEN) after administration of VEN, a CYP2D6 substrate, for determining CYP2D6 metabolic phenotype in healthy adults receiving VEN. The analysis included data from 2 studies in which healthy adults were classified as either EMs or PMs using established methods (1 genotypic and 1 phenotypic) and were then administered VEN at daily dosages ranging from 75 to 150 mg. Blood plasma samples were taken at various time points, and the ODV/VEN ratio was calculated. Blood samples from 28 participants in the 2 studies were available for analysis. The ODV/VEN ratio distinguished the EM and PM phenotypes; ratios were 1 or greater for EMs and less than 1 for PMs at 4 hours after dose administration. The ratio of ODV/VEN is an effective means of phenotyping individuals according to their CYP2D6 metabolizer status.