Patients with depression have more comorbidities than those without depression. The cost of depression-associated comorbidities accounts for the largest portion of the growing cost of depression treatment. Patients with depression have a higher risk of stroke with poor prognoses than those without depression; however, previous studies evaluating the relationship between depression and stroke prognosis have not accounted for surgical treatment or other risk factors. Therefore, we investigated whether depression is a risk factor for mortality in stroke patients with nonsurgical treatment after adjusting for other risk factors.We retrospectively analyzed the data of patients with major depressive disorder (MDD) and age and sex-matched controls without MDD during 1999 to 2005. We then identified patients who developed stroke in both groups and analyzed risk factors for death in these stroke patients who received nonsurgical treatments during a follow-up period from 2006 to 2012.Patients with MDD had higher Charlson Comorbidity Index Scores (CCISs) and exhibited higher frequencies of comorbidities such as diabetes mellitus, hypertension, hyperlipidemia, and coronary heart disease than controls without MDD, and most of MDD patients had very low or high socioeconomic status (SES) and lived in urban settings. Most stroke patients with MDD who received nonsurgical treatment were female, had very low or high SES, and lived in urban settings; in addition, stroke patients with MDD who received nonsurgical treatment had higher CCISs and frequencies of hyperlipidemia and coronary heart disease than those without MDD who received nonsurgical treatment. However, depression was not a risk factor for death in stroke patients with nonsurgical treatment.Hemorrhagic stroke, age, sex, and CCISs were risk factors for death in stroke patients with nonsurgical treatment, but depression did not affect the mortality rate in these patients.