This study evaluated the effectiveness of Rational Emotive Behavior Therapy (REBT) for outpatients with GAD and mild depression and tested the effectiveness of REBT to an active, alternative treatment, Humanistic, Client-Centered Therapy (HCCT) in a clinical setting. The study aimed to understand whether REBT is a more effective treatment than HCCT through testing both pre-treatment and including three-month follow-up results. Thirty-one participants were assessed for overall psychopathological variables such as anxiety, depression, levels of unhealthy negative emotions and regret, activation, hope and nothingness as ontological well-being (OWB) variables before and after a 12 week intervention as well as during a threemonth follow-up. We randomly assigned participants to either REBT or HCCT. The psychotherapists followed strict guidelines to incorporate the distinctive features of REBT. This included educating clients about irrational and rational beliefs, introducing the binary model of emotional distress, using a range of disputing techniques (logical, philosophic, and functional), and discussing alternative rational beliefs such as unconditional acceptance of self, others, and life. The HCCT group was treated with Rogerian techniques such as unconditional positive regard, accepting negative emotions, and reflection. The clients completed the Beck Depression Inventory, Beck Anxiety Inventory, Shortened Attitude and Beliefs Scale, the Ontological Well-being Scale, and the healthy and unhealthy negative emotions scale. The outcomes were analyzed using split plot ANOVA with post hoc, Reliable Change Index, and Clinical Significance Change Index. Although split-plot ANOVA results showed that there was not significant difference in main effect of treatment between REBT and HCCT groups, further detailed analysis such as main effect of time, time by interaction values, Reliable Change Indices, clinically significant change analysis, and post hoc indicated that REBT treatment was more beneficial than HCCT treatment at any of the three time points in most variables. Another experimental study with larger sample is needed to confirm the result in future studies.