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Background Prepectoral implant placement is an innovative option for breast reconstruction, due to multiple advantages over subpectoral implant placement. The adoption of various ADMs and meshes supports the utilization of the prepectoral technique. Methods 200 breasts were reconstructed with prepectoral implant placement after nipple-sparing mastectomy in a one-stage direct-to-implant procedure. The implants were completely covered and fixed with porcine ADMs (Strattice™ or Artia™), or with synthetic meshes (TIGR®). The pectoralis major muscle was not detached at all and kept intact entirely. Results Minor complications included minimal nipple necrosis without further intervention and complete healing in 14 breasts (7.0%). Major complications comprised implant loss due to skin necrosis and wound infection in 7 breasts (3.5%), and hematoma with revision surgery in 8 breasts (4.0%). At a mean follow-up of 36 months cosmetic results were excellent and good in 180 breasts (90.0%), sufficient in 13 breasts (6.5%) and insufficient in 7 breasts (3.5%). Breast animation deformity and implant displacement could not be observed, while implant rotation was documented in 5 breasts (2.5%). Capsular contractures grade III or IV could not be observed neither in patients with previous radiotherapy nor in patients with radiotherapy to the reconstructed breast. Conclusions The single-stage direct-to-implant prepectoral implant placement after NSM with complete coverage of the implant with ADM or synthetic mesh represents a novel and feasible technique for breast reconstruction. This technique provides an alternative to the subpectoral implant placement with excellent cosmetic results avoiding the disadvantages of the subpectoral implant placement. more...