Introduction: The pedicled transverse rectus abdominis musculocutaneous flap (p-TRAM) is a well-established option for autologous breast reconstruction (BR) but donor-site morbidity is still reported. The aim of the present study was to compare donor-site morbidity after reinforcement of the abdominal wall regarding development of bulging or hernia, abdominal muscle strength, complications, and abdominal pain hypothesizing, that reinforcement with acellular dermal matrix (Strattice™) is superior to reinforcement with synthetic mesh (Prolene^®). Materials and methods: A randomized, prospective, double-blind study was conducted with 29 patients admitted for BR with the p-TRAM flap at Department of Plastic Surgery, AUH, Denmark, 2014–2016. Allocation rate 1:1. Follow-up at 4, 12, and 24 months. Results: 24 months postoperatively the computerized tomography verified bulging frequency was 35.7% in the ADM group and 6.7% in the synthetic mesh group (p = 0.11). Two patients (14.3%) in the ADM group and no patients in the synthetic mesh group developed hernia. No significant difference between baseline and 2-year measurement of abdominal muscle strength was observed. Conclusion: The present study did not demonstrate any statistically significant differences between treatment groups regarding risk of bulging or hernia, abdominal muscle strength, complications, pain or pain related QoL within two years of follow-up. Although the small sample size sets limitations for drawing wide conclusions the hypothesis that reinforcement with ADM is superior to synthetic mesh cannot be confirmed. Further research into methods for decreasing donor-side morbidity related to the TRAM flap or other rectus abdominis muscle-based flaps is needed.