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Acne vulgaris (AV) is a common dermatological condition that ranges from mild comedones to severe inflammatory nodules and scarring. Effective management is essential for improving patients' quality of life. The recent FDA approval of IDP-126 (Cabtreo™), a novel triple-combination gel, meets these needs by combining clindamycin phosphate, benzoyl peroxide, and adapalene into a single formulation. This systematic review and meta-analysis aimed to assess the efficacy, safety, and impact of IDP-126 on quality of life in managing AV. The study's goal was to provide clinicians with the necessary information to consider including this medication in acne treatment plans. A total of 281 articles were manually screened, and three studies (n = 388) met the inclusion criteria. Standardized mean differences were used to quantify lesion reductions, while pooled ORs assessed adverse events. Additional references were reviewed to address potential gaps in the reported outcomes. IDP-126 showed significant reductions in inflammatory and non-inflammatory lesions compared to vehicle treatments and demonstrated favorable numbers needed to treat compared to other topical therapies. It was associated with application site pain and erythema. Notable improvements in quality of life were observed across various domains related to acne severity. IDP-126 is an effective treatment for AV, offering substantial clinical benefits and improving quality of life. While it is associated with higher rates of certain adverse effects, its overall efficacy supports its inclusion in treatment regimens, provided that its safety profile is carefully managed to optimize patient outcomes.