OBJECTIVES: Recent studies have found that the use of psychotropic medications in women with coronary artery disease (CAD) led to long-term adverse outcomes such as cardiovascular adverse events.  This study examined the effect of psychotropic medication use on the health-related quality of life (HRQoL) of women with CAD. METHODS: Analysis was conducted using the 2007 Medical and Expenditure Panel Survey (MEPS) database, which is nationally representative of the US civilian non-institutionalized population.  Female patients >=18 years with CAD were included in this analysis.  CAD patients were identified using a combination of International Classification of Diseases (ICD-9) diagnosis codes.  HRQoL was measured using the Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) of the Short-Form 12 Version 2 (SF-12).  HRQoL and sociodemographic characteristics of female CAD patients who used at least one psychotropic medication were compared with those who did not use any psychotropic medications.  Bivariate comparisons were made using t-tests for continuous variables and chi-square tests for categorical variables.  Multivariate comparisons using analysis of covariance (ANCOVA) models were conducted to assess the association of HRQoL with psychotropic use after adjusting for age, race, education, marital status, insurance status, and the number of medical conditions in 2007. RESULTS: Of the 4,253,569 women with CAD in the US, 1,312,413 (30.9%) took psychotropic medications.  Women taking psychotropic medications reported a significantly higher number of medical conditions compared to non-users (13.25 vs. 9.51, p<0.0001).  The mean unadjusted differences in PCS-12 and MCS-12 scores between psychotropic drug users versus non-users suggested worse scores among women taking psychotropic medications (PCS-12: -4.93; p=0.03 and MCS-12: -9.46; p=0.0006), and this trend in differences continued after adjusting for covariates (PCS-12: -2.23; p=0.26 and MCS-12: -7.51; p=0.0034). CONCLUSIONS: Consistent with findings of long-term adverse outcomes from previous studies, psychotropic medication use among women with CAD was associated with significantly worse HRQoL.