Background: Atrophic post-acne scarring constitutes a troublesome cosmetic concern for both patients and dermatologists. Old and new therapies as well as combinations are being introduced to achieve a satisfactory response. Microneedling has been used either alone or under different combinations for its treatment. The aim was to compare its combination with topical platelet-rich plasma versus its combination with topical Botulinum Toxin-A. Methods: 30 subjects with different types and grades of atrophic post-acne scars completed the study. Right side of the face was treated with microneedling and platelet-rich plasma while the left side was treated microneedling and Botox. Response was assessed using two different scales. Patient satisfaction and pain were also assessed. Results: Regarding response to therapy and according to the quartile grading scale, there was no statistically significant difference between the two sides where (23.4% & 13.3%) of the right and left sides, respectively, had an excellent response. Regarding the difference in the qualitative global scarring grading system before and after treatment, there was a highly statistically significant improvement on both sides with higher improvement on the right side than left side but in a non-statistically significant way. Conclusions: Both combinations present efficacious options for treating acne scars with comparable efficacy.