Objective: To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD). Method: Adults (N = 201) with treatment-resistant MDD or BD received repeat-dose IV ketamine treatment at a community-based clinic. Mixed features were measured using symptoms of anxiety, irritability, and agitation (AIA), as measured by the Generalized Anxiety Disorder-7 (GAD-7) scale. The Quick Inventory for Depressive Symptomatology Self-Report-16 (QIDS-SR₁₆) was used to measure overall treatment response, and the QIDS-SR₁₆ suicidal ideation (SI) item was used to measure change in SI symptoms with ketamine treatment. The anxiety, irritability, and agitation items on the GAD-7 were used to assess effectiveness of IV ketamine in treating symptoms of mixed features. Results: In this retrospective analysis, 113 participants met AIA criteria. Participants with AIA experienced a significantly greater reduction in overall depressive symptoms (F(1, 558) = 9.49, P =.002), SI (F(1, 558) = 3.103, P =.079), anxiety (F(1, 198) = 5.52, P =.007), irritability (F(1, 198) = 28.35, P <.001), and agitation as measured by “trouble relaxing” (F(1, 198) = 6.70, P =.010) from baseline compared to the non-AIA group, regardless of number of treatments received. Conclusions: Our preliminary results suggest that IV ketamine is effective in rapidly treating AIA and SI in adults with treatment-resistant mood disorders. This observation suggests that IV ketamine could be considered a treatment alternative for adults with MDD or BD presenting with mixed features.