Background <p>Many causes can lead to acne, such as increased sebum production, altered sebum lipid quality from increased androgen activity, abnormal keratinization of the infundibular epithelium, and Propionibacterium acnes (P. acnes) colonizing the follicles.</p> Aim <p>The present study aimed to evaluate and compare the clinical efficacy of botulinum toxin-A vs. tranexamic acid intradermal injection in the treatment of acne vulgaris.</p> Methods <p>This split face study includes forty patients with varying grades of acne vulgaris. They were injected intradermally with tranexamic acid (20&#xa0;mg/ml) on the left side for three sessions two weeks apart and once with botulinum toxin-A on the right side.</p> Results <p>After treatment, the Total Lesion Count, Comprehensive Acne severity Scale, and Clinical Erythema Assessment Scale significantly reduced, with a greater reduction in erythema on the tranexamic acid side and a greater reduction of comedones on the botulinum toxin side.</p> Conclusion <p>Tranexamic acid and botulinum toxin-A can be promising adjuvants in treating acne vulgaris by their specific mechanisms in the dermatological domain.</p>