Background: Anxiety is a problem that most often occurs in the pre-operative coronary artery bypass graft surgery stage. The combination of prayer therapy with education is expected to be able to overcome anxiety. The combination of prayer and education therapy have been researched as a potential holistic intervention for reducing anxiety in coronary artery bypass graft surgery. Purpose: This study compares the effect of combination therapy with the golden standard of therapy in hospitals. Methods: A true-experimental design was used. Fifty participants were randomly assigned to two groups. Data were collected using a State-Trait Anxiety Inventory questionnaire from Spielberger. Findings: Most respondents were elderly, male, high school graduates in the treatment group, and bachelor graduates in the control group. Prayer therapy and education have an effect of 63.8% on reducing anxiety. An increase of 1 constant in the provision of prayer therapy and education can reduce anxiety by 0.772. Conclusions: The combination of prayer therapy and education becomes the holistic nursing modality that can reduce anxiety in pre-operative coronary artery bypass graft patients. © The Author(s) 2023.