Different treatment options for post-acne scars exist, but with varying clinical efficacy, side effects, and prolonged downtime. This study aims to compare the efficacy and safety of combined subcision with either fractional CO2 laser or cross-linked hyaluronic acid filler (HA) versus subcision alone in the treatment of facial atrophic post-acne scars. Forty patients with atrophic post-acne scars were subjected to subcision on both sides of the face, then were randomly divided into three groups. Group I (20 patients): subcision combined with cross-linked HA filler injection at one side of the face; group II (20 patients): subcision followed by fractional CO2 at the other side of the face; and group III (20 patients): with subcision only as a control group. Treatment sessions were every month until clinical improvement or for maximum three sessions. The treatment’s efficacy was assessed by Goodman and Baron’s qualitative and quantitative grading systems. The two blinded investigator scores showed significant improvement in both the filler side versus subcision (p value = 0.015), and the fractional laser side versus subcision (p value < 0.001), with no statistically significant difference between both sides (p value = 0.171). Qualitative grading by Goodman and Baron scores showed that the percentage of patients with excellent improvement was higher in group 1 and group 2 than in group 3 with p value = 0.031; also the mean percentage of reduction in quantitative grading was higher in group 1 and group 2 than in group 3 with p value < 0.00. Either combined subcision with fractional CO2 laser or with cross-linked HA filler achieved superior improvement in facial atrophic post acne scars treatment with no serious side effects in this study. However, subcision only by blunt canula also had modest improvement.