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Background: Anxiety is a common psychiatric condition in cardio-vascular diseases. Saffron appears to have a wide range of therapeutic effects on psychiatric conditions and cardio-vascular disorders. The aim of this study was to determine the effect of saffron on anxiety in hospitalized patients with acute coronary syndrome (ACS). Materials and Methods: In this clinical investigation, we selected 80 patients with ACS from Tohid Medical Center, Sanandaj. Patients were divided randomly into two groups, intervention group (n = 41), and control group (n = 39), based on how they received saffron and placebo every 12 hours for 4 days, respectively. The Spielberger Anxiety Inventory was completed before and after the intervention in both groups. Results: There was no significant difference between the intervention and control groups regarding the mean scores of the trait and state anxiety before and after the intervention (P > 0.05). Conclusion: The present study did not corroborate the therapeutic effects of saffron on reducing anxiety in patients with ACS.