OBJECTIVES:  The objectives of this study were to identify patterns and predictors of depression treatment in ambulatory settings in the United States (US) among adults with Multiple Sclerosis (MS) and depression. METHODS: A cross-sectional study was conducted by pooling several years (2005-2011) of data from National Ambulatory Medical Care Survey and the outpatient department of the National Hospital Ambulatory Medical Care Survey. The final study sample was identified from ambulatory visits among adults (age ≥ 18 years) with MS and depression. Ambulatory visits with MS were identified by using ICD-9-CM of 340.xx, while visits with depression were identified by ICD-9-CM codes of 296.2-296.36, 300.4 or 311, or if the answer to the question “Regardless of the diagnoses written…..does the patient now have: depression?” was “yes.” Dependent variable of this study was pharmacological treatment for depression with or without psychotherapy. Predictors of depression treatment were ascertained by conducting multivariate logistic regression. Complex survey designs of the datasets were adjusted to obtain nation level estimates. RESULTS:  According to the study findings, between 2005-2011 approximately 2.1 million visits involved a diagnosis of MS and depression. Depression treatment was observed in 57.25% of the study sample. Selective serotonin reuptake inhibitors were the most prescribed antidepressant class, and fluoxetine was the most prescribed individual antidepressant in the study sample. Individuals who were 40 years or older were 81% less likely (Odds Ratio=0.189, 95% CI 0.036-0.997) to receive depression treatment compared those who were in the age group of 18-39 years. With the increase in each chronic condition, the likelihood of receiving depression treatment decreased by 44% (Odds Ratio=0.554, 95% CI 0.335-0.917). CONCLUSIONS:  Approximately six out of ten ambulatory visits involving MS and depression recorded some form of depression treatment. Future longitudinal studies should examine the clinical outcomes associated with depression treatment in this vulnerable population.