Abstract Background Managing acne scars is a challenge and therapies are divided into nonsurgical and surgical. Highly Purified Technology Polynucleotides (PN-HPT) is a compound that contains a mixture of DNA polymers of different lengths. Numerous studies have shown that PN-HPT also serves as an energy source, thus influencing cellular growth and cell vitality. Objectives The authors aimed to assess the improvement in dermal quality and acne scars after PN-HPT vs placebo according to Antera 3D and the patient responses to the patient satisfaction questionnaire after a comparison of pretreatment and posttreatment photographs at 1 and 3 months. Methods Included were women aged 30 to 50 years with grade 3 to 4 moderate-to-severe atrophic scars according to the Goodman classification; nonsmokers; and had not had active acne during the past 5 years. Ten patients (PN-HPT group) were treated with 4.0 mL of PN-HPT, and 10 patients (control) were treated with 4.0 mL of normal saline. All medical treatments were performed in a double-blinded manner; neither the injection doctor nor the patient knew if the PN-HPT or the placebo was being administered. Results Twenty women who fit the inclusion criteria were enrolled in this study. Only patients in the PN-HPT group improved significantly at 1 and 3 months after treatment compared with baseline. Conclusions This prospective and randomized study showed that PN-HPT in monotherapy was safe and effective treatment for atrophic scar acne compared with placebo. Prospective and randomized studies will be necessary to investigate the clinical effectiveness in a larger cohort of patients and for a longer follow-up. Level of Evidence: 2