BACKGROUND: Scars and soft tissue deformities (S-STDs), often resulting from hemifacial atrophy, trauma, and outcomes of burns, were usually associated with hyperpigmentation of overlying skin. OBJECTIVES: This study aimed to evaluate the long-term effects of fat grafting commonly called "Lipofilling" enhanced with adipose-derived mesenchymal stem cells (Lipofilling-AD-MSCs) for treating S-STDs with pigmentary changes. METHODS: A cohort study has been performed. 50 patients affected by S-STDs with hyperpigmentation treated with Lipofilling-AD-MSCs and 50 patients treated with Lipofilling not enhanced (Lipofilling-NE) were prospectively assessed. The pre-op evaluation included a clinical evaluation, a photographic assessment, magnetic resonance imaging, and ultrasound. Post-op follow-up was performed at 1, 3, 7, 12, 24, 48, weeks, and then annually. RESULTS: Improvement in volume contours and pigmentation was clinically assessed. All people who underwent the treatments (Lipofilling-AD-MSCs and Lipofilling-NE) were satisfied with the improving pigmentation, texture, and volume contours with some differences. However, the results reported displaying a better trend in patients treated with Lipofilling-AD-MSCs to be more satisfied than patients treated with Lipofilling-NE (p < 0.0001). CONCLUSIONS: In conclusion, Lipofilling-AD-MSCs was the preferred option for improving the contour deformities related to increased pigmentation of scars. LEVEL OF EVIDENCE IV: Evidence obtained from cohort studies.