Major depressive disorder (MDD) is a condition that is difficult to treat, as many individuals do not experience complete remission, and many eventually relapse. Individuals who do not respond to antidepressant therapy are defined as having treatment-resistant depression (TRD). The epidemiology of TRD has been studied using commercial insurance claims data in the United States, but no such studies exist for a general population or in Canada. This thesis describes the epidemiology of TRD in Manitoba between 1996 and 2016 and compares the risks for ambulatory visits, emergency department (ED) visits, hospitalizations, and all-cause mortality for individuals with TRD to those with non-treatment-resistant MDD. I used the Anderson-Gill generalization of the extended Cox proportional hazards model to analyze these risks. TRD was defined using the Massachusetts General Hospital Staging Method (MGH-s), where scores of 2.5 and higher correspond to TRD. I identified 169,511 adults living in Manitoba between 1996 and 2016 who were diagnosed with MDD and dispensed at least six weeks of antidepressants from the Manitoba Population Research Data Repository at the Manitoba Centre for Health Policy. By 2016, 18,663 individuals (11.0% of the cohort) met the criteria for TRD. Compared to MGH-s scores of 1, the hazard ratios (HR) for mental health related ED visits for MGH-2.5 and MGH-3 were 3.9 and 5.6 , respectively. The HR for hospitalizations with a primary diagnosis of MDD were 4.9 and 8.3 for MGH-2.5 and MGH-3, respectively. For individuals 10 years below the average age of the cohort, TRD was associated with a three-fold increased risk for all-cause mortality. For individuals 10 years above the average age of the cohort, TRD was associated with a two-fold increased risk for all-cause mortality. These findings show that TRD is an important risk factor for requiring more intensive medical care for mood and anxiety disorders. Increasing hazards associated with increases in MGH-s scores support the hypothesis that TRD follows a severity continuum. As the risk for all-cause mortality was higher for individuals with TRD, further research is needed to determine whether TRD is associated with a higher risk for suicide.