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Background and Objective: Recently, a novel acne treatment based on selective photothermolysis of pilosebaceous units with follicular delivery of inert gold microparticles as an exogenous chromophore and diode laser pulses has been developed. To evaluate the efficacy and safety of a single monotherapy treatment regimen with gold microparticles and diode laser exposure in patients with moderate and moderately severe acne. Further, to evaluate the added benefit of a second treatment regimen combined with pharmaceutical acne treatment in patients with inadequate initial response., Materials and Methods: Patients with moderate and moderately severe facial acne were recruited in this open-label, pilot study. A single treatment regimen consisted of three weekly facial treatments with topically applied gold microparticles and diode laser pulses. Outcome measures were the proportion of patients with ≥40% improvement in number of acne lesions (weighted lesion count [WLC]) at 12 weeks (single treatment regimen, primary outcome measure), 24, and 36 weeks from baseline (two treatment regimens), safety, and patient satisfaction., Results: A total of 28 patients were enrolled in the study (18 males, 10 females, 19 patients with moderate acne severity, 9 with moderately severe, mean age: 19.8 years). Twenty-five patients underwent analysis for outcome measures. After a single monotherapy treatment regimen, 76% patients (19/25) achieved ≥40% reduction in WLC (mean WLC reduction: 63%; SD: 13%). Of the patients undergoing two treatment regimens (n = 9 patients), 56% experienced a reduction in acne lesion burden (WLC) ≥40% at 24 weeks and 89% 36 weeks post-baseline. Mean pain score was 4.0 (SD: 1.3), and transient erythema and perifollicular edema were commonly noted after treatment. Most patients (81%) were either "satisfied" or "very satisfied" with the treatment., Conclusion: Acne therapy based on selective photothermolysis with gold microparticles shows promise and may be used in treatment of moderate to moderately severe acne. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)