This parallel randomized controlled trial aimed to evaluate the effect of acceptance and commitment therapy (ACT) focused on disrupting repetitive negative thinking (RNT) versus a waitlist control (WLC) in the treatment of depression and generalized anxiety disorder (GAD). Forty-eight participants with a main diagnosis of depression and/or GAD were allocated by means of simple randomization to a 2-session RNT-focused ACT intervention or to the WLC. The primary outcomes were emotional symptoms as measured by the Depression, Anxiety, and Stress Scales-21. Process outcomes included ACT- and RNT-related measures: general RNT, experiential avoidance, cognitive fusion, values, and generalized pliance. At the 1-month follow-up, linear mixed effects models showed that the intervention was efficacious in reducing emotional symptoms (d = 2.42, 95% confidence interval [1.64, 3.19]), with 94.12% of participants in the RNT-focused ACT condition showing clinically significant change in the Depression, Anxiety, and Stress Scales-21 total scores versus 9.09% in the WLC condition (70% vs. 8% in intention-to-treat analysis). The intervention effects were maintained at the 3-month follow-up. No adverse events were found. A very brief RNT-focused ACT intervention was highly effective in the treatment of depression and GAD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).