ImportanceA transdiagnostic treatment, the Unified Protocol, is as effective as single diagnostic protocols in comorbid emotional disorders in clinical populations. However, its effects on posttraumatic stress disorder and other emotional disorders in individuals living in war and armed conflict contexts have not been studied.ObjectiveTo evaluate the efficacy of a cultural and contextual adaptation of the Unified Protocol (CXA-UP) on posttraumatic stress disorder, anxiety, and depression compared to waitlist control in individuals exposed to armed conflict in Colombia.Design, Setting, and ParticipantsFrom April 2017 to March 2020, 200 participants 18 years and older were randomly assigned to the CXA-UP or to a waitlist condition. CXA-UP consisted of 12 to 14 twice-a-week or weekly individual 90-minute face-to-face sessions. Outcomes were assessed at baseline, posttreatment, and 3 months following treatment. Analyses were performed and compared for all randomly allocated participants (intent-to-treat [ITT]) and for participants who completed all sessions and posttreatment measures (per protocol [PP]). The study took place at an outpatient university center and included individuals who were registered in the Colombian Victims Unit meeting DSM-5 diagnostic criteria for posttraumatic stress disorder, anxiety, or depression or were severely impaired by anxiety or depression. Individuals who were receiving psychological therapy, were dependent on alcohol or drugs, were actively suicidal or had attempted suicide in the previous 2 months, had psychosis or bipolar disorder, or were cognitively impaired were excluded.InterventionCXA-UP or waitlist.Main Outcomes and MeasuresPrimary outcomes were changes in anxiety, depression, and somatic scores on the Patient Health Questionnaire and Posttraumatic Stress Disorder Checklist for DSM-5.ResultsAmong the 200 participants (160 women [80.0%]; 40 men [20.0%]; mean [SD] age, 43.1 [11.9] years), 120 were randomized to treatment and 80 to waitlist. Results for primary outcomes in the ITT analysis showed a significant pretreatment-to-posttreatment reduction when comparing treatment and waitlist on the posttraumatic stress disorder checklist for DSM-5 scores (slope [SE], −31.12 [3.00]; P < .001; Cohen d, 0.90; 90% CI, 0.63-1.19), 9-item Patient Health Questionnaire (PHQ-9) (slope [SE],−11.94 [1.30]; P < .001; Cohen d, 0.77; 90% CI, 0.52-1.06), PHQ-anxiety (slope [SE], −6.52 [0.67]; P < .001; Cohen d, 0.82; 90% CI, 0.49-1.15), and PHQ-somatic (slope [SE], −8.31 [0.92]; P < .001; Cohen d, 0.75; 90% CI, 0.47-1.04).Conclusions and RelevanceIn this study, significant reductions and large effect sizes in all measures of different emotional disorders showed efficacy of a single transdiagnostic intervention in individuals exposed to armed conflicts.Trial RegistrationClinicalTrials.gov Identifier: NCT03127982