BACKGROUND: Depression is prevalent in patients receiving hospice care. Standard antidepressant medications do not work rapidly enough in this setting. Evidence suggests that ketamine rapidly treats treatment refractory depression in the general population. Ketamine׳s role for treating depression in the hospice population warrants further study. METHODS: A retrospective medical record review of 31 inpatients receiving hospice care who received ketamine for depression on a clinical basis was conducted. The primary outcome measure was the Clinical Global Impression Scale, which was used retrospectively to rate subjects׳ therapeutic improvement, global improvement, and side effects from ketamine over 21 days. Additionally, time to onset of therapeutic effect was analyzed. RESULTS: Using the Clinical Global Impression Scale, ketamine was found to be significantly therapeutically effective through the first week after ketamine dosing (p < 0.05), with 93% of patients showing positive results for days 0-3 and 80% for days 4-7 following ketamine dosing. Patients experienced global improvement during all 4 studied time periods following ketamine dosing (p < 0.05). Significantly more patients had either no side effects or side effects that did not significantly impair functioning at each of the 4 assessed time periods following ketamine dosing (p < 0.05). Additionally, significantly more patients experienced their first therapeutic response during days 0-1 following ketamine dosing (p < 0.001) than during any other time period. CONCLUSIONS: These data suggest that ketamine may be a safe, effective, and rapid treatment for clinical depression in patients receiving hospice care. Blinded, randomized, and controlled trials are required to substantiate these findings and support further clinical use of this medication in hospice settings.