Objective-Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacological interventions that could address this problem. Ketamine, an Nmethyl-D-aspartate (NMDA) antagonist, has been reported to have antidepressant effects within hours. We examined the effects of a single dose of ketamine on suicidal ideation in subjects with treatment-resistant major depressive disorder (MDD).Method-Thirty-three subjects with DSM-IV-diagnosed MDD received a single open-label infusion of ketamine (0.5 mg/kg) and rated at baseline, 40, 80, 120, and 230 minutes post-infusion with the Scale for Suicide Ideation (SSI), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Rating Scale (HDRS), and the Beck Depression Inventory (BDI).Results-Suicidal ideation scores decreased significantly on the SSI as well as on the suicide subscales of other rating instruments within 40 minutes; these decreases remained significant through the first four hours post-infusion (p<.001). Ten subjects (30%) had a SSI score 4 at baseline, and all dropped below a score of 4 (nine by 40 minutes and one by 80 minutes). For those starting below a score of 4 on the SSI, only one reached a score of 4. Depression, anxiety, and hopelessness were significantly improved at all time points (p<.001).Conclusion-Suicidal ideation in the context of MDD improved within 40 minutes of a ketamine infusion and remained improved for up to four hours post-infusion. Future studies with ketamine in suicidal ideation are warranted due to its potential impact on public health.