Literature provides a moderate level of evidence for the beneficial effects of incisional negative pressure wound therapy (iNPWT) on scar quality. The purpose of this study was to establish if iNPWT results in improved scar outcomes in comparison to the standard of care. Therefore, a within-patient randomised controlled, open-label trial was conducted in transgender men undergoing gender-affirming mastectomies. A unilateral side was randomised to receive iNPWT (PICO™, Smith&Nephew) without suction drains and contrastingly the standard dressing (Steri-Strips™) with suction drain. Scar quality and questionnaires were bilaterally measured by means of objective assessments and patient-reported outcome measures (PROM) at 1, 3 and 12 months. Objective scar outcomes were scar pliability (Cutometer®), colouration (DSM-II) and scar width (3-D imaging). PROM outcomes were related to scars (POSAS and SCAR-Q) and body satisfaction (BODY-Q). From 85 included patients, 80 were included for analyses. No significant difference between treatments was seen in the quantitative outcomes of scar pliability, colour, and width. For qualitative scar outcomes, several significant findings for iNPWT were found for several subscales of the POSAS, SCAR-Q, and BODY-Q. These effects could not be substantiated with linear mixed-model regression, signifying no statically more favourable outcome for either treatment option. In conclusion, this study demonstrated that some PROM outcomes were more favourable for the iNPWT compared to standard treatment. In contrast, the quantitative outcomes showed no beneficial effects of iNPWT on scar outcomes. This suggests that iNPWT is of little benefit as a scar-improving therapy.