Background Given that most patients with moderate to severe acne develop post‐acne scars, many treatment modalities can be used to ameliorate scaring; chemical peels, surgical excision, dermabrasion, fat transfer, autologous collagen, punch grafting, diverse filler injection, and lasers. Microneedling is one of the promising modalities based on the breaking of dermis‐damaged collagen and enhancing new collagen formation. Microbotox (Mesobotox) injection may have a beneficial effect by causing muscular paralysis with subsequent dermal edema due to transient and mild lymphatic insufficiency. The comparison between these two modalities has not been yet assessed. The aim of this study was to evaluate and compare the safety and efficacy of both methods (Microbotox and microneedling) in the treatment of atrophic post‐acne scars. Methods Between May 2021 to April 2022, patients with atrophic post‐acne scars were selected from the out‐patients clinics of the Department of Dermatology, Faculty of Medicine. The face was divided into two sides: the right side was treated with Mesobotox for three sessions once monthly and followed up 3 months later after the last session and the left side was treated with dermapen (microneedling) for six sessions every 2 weeks and followed up 3 months after the last session. The feasibility, safety, and efficacy of both lines of treatment were studied. Results This study included 20 patients with atrophic post‐acne scars. They were 13 females (65%) and 7 males (35%), and their ages ranged between 15 and 35 years with a mean ± sd age of 24.40 ± 5.90 based on the significant improvement between S1 (baseline acne scar score) and both S2 (acne scar score at end of treatment) and S3 (acne scar score 3 months after the last session). Microneedling showed also similar results to Mesobotox. Conclusions Microbotox and microneedling were effective and tolerated.