OBJECTIVES To investigate the off-label prescribing rates of antidepressants among office-based physicians and hospital outpatient department clinics during 2003-2005. METHODS The National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) were used as data sources. Patients who received an antidepressant during the study period were included in the study. Corresponding diagnosis were analyzed to identify off-label prescribing based on Physician Desk Reference and Micromedex. Binary Logistic Regression Analysis was used to predict off-label use on the basis of patient's demographic characteristics and payment methods. Microsoft Access and SPSS 14 were used to analyze the data. RESULTS From 2003 to 2005, a total of 172,489 patient records were collected, of which, 12,251 patient records were included in the study. A total of 7,068 (57.6%) out of 12,251 antidepressant prescriptions were identified as off-label prescriptions in the 3 years. There were 21 different antidepressants were identified in the databases. Amitriptyline HCl, a TCA/SNRI, had the highest off-label prescription rate among all the antidepressants. According to patient demographics characteristics, the odds of receiving antidepressants off-label were found to be increased with age, elderly adult patients are 2 to 4 times (OR = 3.241, 95% CI = 2.727-3.852) more likely to get an off-label prescription of antidepressants than children/adolescents. Whites were considered 1.2 times more likely to receive an off-label prescription of antidepressant than non-whites (OR = 1.218, 95% CI = 1.090-1.361) and 71.7 % Medicare patients were received off-label antidepressant prescription. CONCLUSIONS Off-label prescribing of antidepressants is highly prevalent, especially in TCA/SNRI class of antidepressants. White elderly adults were more likely to get off-label prescriptions than non-whites adults. Future studies are required to address the questions of legal, clinical and economic aspects of off-label prescribing of antidepressants.