Background:Subpectoral implant reconstruction (SIR) is associated with animation deformity and increased postoperative pain. The aim of our study was to compare the short- to medium-term outcome of prepectoral implant reconstruction (PIR) and SIR with acellular dermal matrix.Methods:A review of prospectively collected data of patients who underwent PIR and SIR using biological mesh by a single surgeon between Nov 2016 and Nov 2020 was done. Presentation, smoking history, BMI, bra size, radiology size, pathology data, mastectomy weight, implant volume, radiation treatment, and outcomes were analyzed. For intergroup comparisons, the data were analyzed using Pearson chi-square test and the Student t-test. P values of less than 0.05 were considered statistically significant.Results:Eighty-two patients had 109 implant reconstructions (85 PIR and 24 SIR). Median follow-up was 27 months (4–53). Twenty-five of PIR and six of SIR were risk reduction surgeries. Two groups were comparable except for significantly higher percentage of node positive (13/18, 72% versus 20/60, 33%; P = 0.003), Her 2-positive disease (7/18, 39% versus 9/60, 15%; P = 0.027), and radiotherapy (15/24, 63% versus 21/85, 25%; P = 0.001) in SIR. There was no statistically significant difference between the two groups with regard to hematoma, wound infection, red reaction, seroma needing aspiration, wound necrosis, and implant loss. Significantly more patients in the prepectoral group had rippling needing fat grafting (n = 13, 15% versus 0; P = 0.041) and significantly more patients in the subpectoral group had fat grafting for contour deformity (n = 6, 25% versus n = 6, 7%; P = 0.025).Conclusion:PIR is comparable to conventional SIR with regard to most of the complications.