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We conducted a randomized, controlled trial (RCT) to investigate our hypothesis that the interactive chatbot, Vitalk, is more effective in improving mental wellbeing and resilience outcomes of health workers in Malawi than the passive use of Internet resources. For our 2-arm, 8-week, parallel RCT (ISRCTN Registry: trial ID ISRCTN16378480), we recruited participants from 8 professional cadres from public and private healthcare facilities. The treatment arm used Vitalk; the control arm received links to Internet resources. The research team was blinded to the assignment. Of 1,584 participants randomly assigned to the treatment and control arms, 215 participants in the treatment and 296 in the control group completed baseline and endline anxiety assessments. Six assessments provided outcome measures for: anxiety (GAD-7); depression (PHQ-9); burnout (OLBI); loneliness (ULCA); resilience (RS-14); and resilience-building activities. We analyzed effectiveness using mixed-effects linear models, effect size estimates, and reliable change in risk levels. Results support our hypothesis. Difference-in-differences estimators showed that Vitalk reduced: depression (-0.68 [95% CI -1.15 to -0.21]); anxiety (-0.44 [95% CI -0.88 to 0.01]); and burnout (-0.58 [95% CI -1.32 to 0.15]). Changes in resilience (1.47 [95% CI 0.05 to 2.88]) and resilience-building activities (1.22 [95% CI 0.56 to 1.87]) were significantly greater in the treatment group. Our RCT produced a medium effect size for the treatment and a small effect size for the control group. This is the first RCT of a mental health app for healthcare workers during the COVID-19 pandemic in Southern Africa combining multiple mental wellbeing outcomes and measuring resilience and resilience-building activities. A substantial number of participants could have benefited from mental health support (1 in 8 reported anxiety and depression; 3 in 4 suffered burnout; and 1 in 4 had low resilience). Such help is not readily available in Malawi. Vitalk has the potential to fill this gap., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kleinau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)