Antidepressants are among the most widely prescribed medications, yet only 35-45% of patients achieve remission following an initial antidepressant trial. The financial burden of treatment failures in direct treatment costs, disability claims, decreased productivity, and missed work may, in part, derive from a mismatch between optimal and actual prescribed medications. The present 1 year blinded and retrospective study evaluated eight direct or indirect health care utilization measures for 96 patients with a DSM-IV-TR diagnosis of depressive or anxiety disorder. The eight measures were evaluated in relation to an interpretive pharmacogenomic test and reporting system, designed to predict antidepressant responses based on DNA variations in cytochrome P450 genes (CYP2D6, CYP2C19, CYP2C9 and CYP1A2), the serotonin transporter gene (SLC6A4) and the serotonin 2A receptor gene (5HTR2A). All subjects had been prescribed at least one of 26 commonly prescribed antidepressant or antipsychotic medications. Subjects whose medication regimen included a medication identified by the gene-based interpretive report as most problematic for that patient and are in the 'red bin' (medication status of 'use with caution and frequent monitoring'), had 69% more total health care visits, 67% more general medical visits, greater than three-fold more medical absence days, and greater than four-fold more disability claims than subjects taking drugs categorized by the report as in the green bin ('use as directed') or yellow bin ('use with caution'). There were no correlations between the number of medications taken and any of the eight healthcare utilization measures. These results demonstrate that retrospective psychiatric pharmacogenomic testing can identify past inappropriate medication selection, which led to increased healthcare utilization and cost.