Many healthcare workers on the frontlines of the COVID-19 pandemic are experiencing clinical levels of mental health symptoms. Evidence-based interventions to address these symptoms are urgently needed. RESTORE (Recovering from Extreme Stressors Through Online Resources and E-health) is an online guided transdiagnostic intervention including cognitive-behavioral interventions. It was specifically designed to improve symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) associated with COVID-19-related traumatic and extreme stressors. The aims of the present study were to assess the feasibility, acceptability, and initial efficacy of RESTORE in healthcare workers on the frontline of the COVID-19 pandemic. We conducted an initial uncontrolled trial of RESTORE in 21 healthcare workers who were exposed to COVID-19-related traumatic or extremely stressful experiences in the context of their work and who screened positive for clinical levels of anxiety, depression, and/or PTSD symptoms. RESTORE was found to be feasible and safe, and led to statistically significant and large effect size improvements in anxiety, depression, and PTSD symptoms over the course of the intervention through follow-up. RESTORE has the potential to become a widely disseminable evidence-based intervention to address mental health symptoms associated with mass traumas.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov ID: NCT04873622