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Recurrent ptosis is a common sequel of mastopexy. The use of mesh as an adjunct to the double-skin technique was developed to reduce the incidence of recurrent ptosis. The optimal mesh needs to strike the right balance between persistence, inflammation, biocompatibility, and incorporation without interfering with mammography or presenting a long-term infection risk. This study investigated the ability of a biologic tissue matrix, FortaPerm, to achieve these goals. Women undergoing mastopexy were enrolled in this prospective observational study. The study participants were evaluated at multiple time points for 5 years. Efficacy was assessed primarily by photographic evaluation and secondarily by mammography, patient and physician global assessments, and patient pain assessments. Five women ages 17–41 years were enrolled in this study. At 12 months, 80% of the patients (4/5), and at 5 years, 66% of the patients (2/3) had no asymmetry or ptosis. Mammographic evaluation of the breasts was not affected by the presence of the FortaPerm, and there were no abnormal findings. In two patients, FortaPerm was associated with bilateral seromas associated with extrusion of small amounts of the FortaPerm material in the absence of surrounding inflammation. FortaPerm achieved excellent initial aesthetic outcomes and long-term maintenance of the breast position with no evidence of ptosis 5 years postoperatively for a majority of the patients. FortaPerm did not interfere with mammography, presented no long-term safety concerns, and produced satisfactory results for all patients relative to appearance of the scar as well as shape and firmness of the breasts.