Background: Conventional isotretinoin dosing (0.5–1.0 mg/kg/day) for acne vulgaris achieves high efficacy, but is limited by significant adverse effects. Low-dose regimens (≤ 0.5 mg/kg/day) may offer an improved therapeutic ratio.

Objectives: To evaluate the efficacy, safety, and relapse outcomes of a flexible low-dose isotretinoin protocol in Iraqi adolescents and young adults.

Methods: A prospective single-arm study involving 72 patients aged 14–25 years) with mild-to-severe acne vulgaris received isotretinoin 0.1–0.5 mg/kg/day for 16–20 weeks. The study was conducted at the Dermatology Outpatient Clinic of Al-Diwaniyah Teaching Hospital, Iraq, between January 2023 and December 2024. The clinical response was assessed using the Investigator's Global Assessment. Safety was monitored via adverse events and laboratory tests for liver function and lipid profile. The patients were followed for 6–12 months for relapse assessment. Data were analyzed using the SPSS software and presented using descriptive statistics.

Results: Treatment success was achieved in 88.9% (64/72) of the patients. Adverse events were mild including cheilitis (97.2%), xerosis (4.2%), myalgia (2.8%), dry eyes (4.2%), and transient headache (2.8%). No mood alterations or severe skin reactions occurred. No significant laboratory abnormalities were noted. During follow-up, 27.8% (20/72) relapsed; all successfully completed a second identical low-dose course.

Conclusion: Low-dose isotretinoin demonstrates high efficacy and safety. Even as relapse rates are higher than with conventional dosing, the good tolerability supports its use as a first-line strategy, with re-treatment being a viable option.