Therapeutic dogma has been to treat acne scars with ablative fractional laser no less than 6 months after isotretinoin (ITN) cessation. To evaluate the safety and efficacy of fractional ablative CO laser (FACL) in patients treated concurrently with ITN. We conducted a prospective split-face randomized control trial in patients treated with FACL concurrently with ITN versus patients treated with FACL 6 months post-ITN treatment. Patients received 3 monthly sessions of FACL with concurrent ITN treatment on half of the face; the other side of the face received the same FACL treatment regimen 6 months post-ITN cessation. Patients were followed for adverse effects up to 6 months post-FACL treatment. Final cosmesis was scored using the Quantitative Global Acne Scarring Grading System (GASGS) by three independent dermatologists. The GASGS of the concurrent ITN-FACL treated side of the face was significantly lower than the side treated with delayed laser therapy (4.7 ± 2.5 vs. 7.7 ± 2.9, respectively, p < 0.001). The laser's settings were standardized, and not adjusted per patient skin type. Per our prospective trial, concurrent treatment of FACL -ITN is superior to delayed FACL treatment 6 months post-ITN cessation. Fractional ablative laser treatment is effective in improving acne scars, which persist despite isotretinoin therapy.