Acute skin defects often cause many adverse events such as abnormal pigmentation and scar formation, the satisfactory healing of which remains a significant clinical challenge. Over the past several decades, a number of skin equivalents have been available for clinical purposes to promote wound closure. However, the true values of skin equivalent - tissue-engineered skin (TE-skin) composed of neonatal fibroblasts and keratinocytes - in improving the quality of wound healing are not yet elucidated. A total of 158 patients were enrolled, 129 of which were used in this study. In these patients, acute skin defects were treated with TE-skin as experimental group, and treated with Vaseline primary dressing as control group. The differences in average healing times between the two groups were determined with statistical analysis according to different depths of skin defects. Wound quality, including pigmentation, cicatrization, and pliability, was assessed by investigators from different clinical centers over a 6-month period. The cosmetic outcome of the wound was further evaluated with histological method. In the study, the average time of wound closure in the experimental group was significantly shortened by 6.5 to 20 days according to different depths of skin defects. The cosmetic quality of reconstructed skin was satisfactory, with the patients enjoying better pliability, less abnormal pigmentation, and cicatrization. Safety analysis demonstrated that the wounds treated with TE-skin did not show clinical or laboratory evidence of rejection during the trial. These results indicate that TE-skin is a suitable and clinically effective treatment for various acute skin defects. Furthermore, the TE-skin appears to produce more satisfactory cosmetic results when compared with the conventional therapy.