Background <p>Skin hyperpigmentation, caused by excessive melanin production, presents both aesthetic and psychological concerns. The Q-switched Nd:YAG laser is a key treatment modality, with effectiveness influenced by factors such as skin type, laser fluence, and treatment frequency. A multimodal approach combining laser therapy and medical treatment may enhance outcomes.</p> Objectives <p>This study evaluates the efficacy and safety of Q-switched Nd:YAG laser combined with medical therapy for hyperpigmentation, focusing on clinical outcomes and patient satisfaction.</p> Methods <p>A randomized cross-sectional study was conducted on 300 patients in private clinics from January 2022 to September 2023. Treatment response was assessed through clinical evaluations and patient-reported satisfaction using the Likert scale. The impact of factors such as gender, sun exposure, pregnancy, and hormonal influences was analyzed.</p> Results <p>The majority of participants were female (92.6%). Clinical evaluation and patient satisfaction improved significantly over successive sessions, with "Good" satisfaction ratings increasing from 80.6% initially to 98.3% at study completion. Male patients demonstrated a stronger response to treatment than females. No significant impact of the studied factors on outcomes was identified.</p> Conclusions <p>A comprehensive assessment of hyperpigmentation is crucial for optimal treatment selection. A multimodal approach combining Q-switched Nd:YAG laser and medical therapy yields superior results compared to single-modality treatments, with outcomes improving progressively across sessions.</p> Level of Evidence III <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors &#xa0;<a href="http://www.springer.com/00266">www.springer.com/00266</a>.</p>