Background: A previous multi-center clinical study of low energy (20% power), single-pass helium plasma dermal resurfacing (HPDR) showed positive results but did not fully reveal the true potential of this novel technology. A second multi-center clinical study, reported herein, was therefore undertaken to evaluate efficacy and safety of high energy (40%), double pass HPDR for treatment of facial rhytids (ClinicalTrials.gov Identifier: NCT04185909). Methods: Fifty-five eligible subjects seeking improvement in facial rhytids were enrolled for study at one of four investigational sites. All subjects underwent fullface HPDR treatment. The forehead, nose, cheeks, and peri-oral treatment zones were treated at 40% power with two passes whereas the peri-orbital and jawline/ mandibular zones were treated at 20% power (up to 40% for jawline/mandibular zone) and one or two passes. Photographic images of the face were captured using the VISIA-CR system. Three-month posttreatment Fitzpatrick Wrinkle and Elastosis Scale (FWS) scores were compared to baseline scores as determined by blinded independent photographic reviewers (IPRs) and study investigators.Results: Blinded IPRs and study investigators observed a ≥1-point FWS improvement in 100% of subjects with mean change in IPR FWS from baseline to the 90-day visit of −3.6 (±1.2). 96.4% of subjects indicated "improvement" in appearance at the 90-day visit utilizing the modified Global Aesthetic Improvement Scale. Evaluation of VISIA-CR data revealed statistically significant improvements in wrinkles, brown spots, and pore counts. Overall, 269 Adverse Events in 55 subjects were reported; most were mild-moderate in severity (99.3%), anticipated (86.2%), and of relatively short duration with most having resolved within 30 days (60.6%) of treatment. Conclusion: Treatment of facial rhytids with high energy, double pass HPDR as detailed herein enables a marked improvement in FWS that parallels or surpasses competing technologies. VISIA-CR analysis demonstrates additional improvements in skin quality with statistically significant quantitative improvements in brown spots and enlarged pores as well as wrinkles. Effective rhytid effacement combines with high subject satisfaction and few unanticipated adverse events for a reasonable benefit-risk ratio.