INTRODUCTION: This prospective, single-arm pharmacodynamic study assessed the effect of colchicine (COLC) [Strides Pharma UK Ltd, Watford, Hertfordshire, England] 0.5 mg administered orally once daily for 14 days on platelet reactivity with respect to aspirin reaction units (ARUs) and P2Y METHODS: Twenty-two patients with stable coronary artery disease (CAD) on dual antiplatelet therapy (DAPT) with daily maintenance aspirin and clopidogrel were recruited. Baseline platelet function was evaluated with the VerifyNow™ ARU and PRU assays (Werfen, Bedford, MA, USA) and assessed post-completion of COLC 0.5 mg once daily for 14 days. RESULTS: In this study, the median ARU baseline score was 463, and post-COLC it was 436, which was not statistically significant (p = 0.485). The mean difference in scores was -18.31 (95% confidence interval [CI] -74.34 to 37.71, p = 0.504). At baseline, 27.3% of the patients had "aspirin resistance" or were non-responders, compared to 13.6% post-COLC (p = 0.423). The median baseline PRU score was 210, and post-COLC it was 199, which was also not statistically significant (p = 0.581). The mean difference in scores was -7.31 (95% CI -31.1 to 16.5, p = 0.530). At baseline, 50% of the patients had "clopidogrel resistance" or were non-responders, compared to 45.5% post-COLC (p = 0.999). Two patients experienced mild gastrointestinal upset during the trial without interruption of COLC, and there were no serious adverse events or treatment-emergent adverse events. CONCLUSIONS: There were no significant differences in ARUs and PRUs post-COLC trial in patients with stable CAD. This pilot pharmacodynamic study could be clinically informative in patients on DAPT. Further studies are required to confirm these exploratory findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06567678, prospectively registered 20/8/2024.