Objectives: To evaluate the comparative efficacy of Trial-Based Cognitive Therapy (TBCT), Mindfulness-Based Health Promotion (MBHP), and Positive Psychotherapy (PP) for COVID-19-related PTSD. This was the first randomized clinical trial to compare these three distinct approaches in a fully online format during a global health crisis. Method: This single-blind, three-arm randomized controlled trial was conducted online. Fifty-seven patients (94.7% women; mean age = 43.09 years) with COVID-19-related PTSD received 14 weekly individual, therapist-guided online sessions. Assessments occurred at baseline, mid-treatment, and post-treatment. The primary outcome was PTSD symptom reduction (CAPS-5); secondary outcomes included anxiety, depression, and well-being. Results: All three treatments yielded significant within-group reductions in PTSD symptoms (large effect sizes, d > 0.8). However, no significant between-group differences emerged after correction for multiple comparisons, indicating equivalent efficacy. Reductions in trauma-related guilt and dysfunctional beliefs mediated symptom improvement across all groups. Conclusions: TBCT, MBHP, and PP may all be effective individually delivered online PTSD interventions, with no clear evidence of superiority for any single approach. Findings support the feasibility individual virtual care, suggesting treatment selection could be guided by patient preference and clinician expertise rather than assumed differential efficacy. However, the study’s reduced sample size and high dropout rate (57.9%) significantly limit statistical power and generalizability. Adequately powered replication studies are essential to establish definitive comparative effectiveness. Preregistration: ClinicalTrials.gov; NCT04852770.