OBJECTIVE: To study the independent and interactive effects of depression and anxiety symptoms as predictors of cardiovascular disease (CVD) events in a sample of women with suspected myocardial ischemia. Symptoms of depression and anxiety overlap strongly and are independent predictors of CVD events. Although these symptoms commonly co-occur in medical patients, little is known about combined effects of depression and anxiety on CVD risk. METHOD: A total of 489 women completed a baseline protocol including coronary angiogram, CVD risk factor assessment, and questionnaire-based measures of depression and anxiety symptoms, using the Beck Depression Inventory (BDI) and State Trait Anxiety Inventory (STAI), respectively. Participants were followed for a median 5.9 years to track the prevalence of CVD events (stroke, myocardial infarction, heart failure, and CVD-related mortality). We tested the BDI × STAI interaction effect in addition to the BDI and STAI main effects. RESULTS: Seventy-five women (15.3% of sample) experienced a CVD event, of which 18 were deaths attributed to cardiovascular causes. Results using Cox regression indicated a significant BDI × STAI interaction effect in the prediction of CVD events (p =.02) after covariate adjustment. Simple effect analyses indicated that depression scores were significant predictors of CVD events among women with low anxiety scores (hazard ratio [HR] = 2.3 [in standard deviation units]; 95% Confidence Interval [CI] = 1.3-3.9; p =.005) but not among women with higher levels of anxiety (HR = 0.99; 95% CI = 0.70-1.4; p =.95). CONCLUSION: Among women with suspected myocardial ischemia, the value of depression symptoms for predicting CVD events varied by the severity of comorbid anxiety. These results suggest that the clinical utility of depression measures may be improved by using them in combination with measures of anxiety. Copyright © 2009 by the American Psychosomatic Society.