Background The acellular dermal matrix (ADM)-assisted breast reconstruction technique is widely known, but discouraging results due to early postoperative complications have been reported. As the literature identifies seroma as the most common issue after breast surgery without identifying its pathogenesis, we aimed to report the trend of postoperative daily serum collection after ADM-assisted breast reconstruction and compare it with data in the literature in order to discover more about this little-known topic. Methods A retrospective study on 28 consecutive patients who received ADM-assisted breast reconstruction between February 2013 and February 2014 was performed. In order to reduce the number of variables that could affect serum production, only one brand of ADM was used and all tissues were handled gently and precisely. The daily drainage volume was recorded per patient during the first four days of hospitalization. Likewise, postoperative complications were noted during routine follow-up. Results In total, five (17.9%) bilateral and 23 (82.1%) unilateral ADM-assisted breast reconstructions (33 implants) were performed. The mean age, body mass index, and length of hospital stay were 53.6 years, 21.3 kg/m², and 4.5 days, respectively. One major complication led to implant loss (3.0%), and nine minor complications were successfully treated with ambulatory surgery (27.3%). Serum collection linearly decreased after 24 hours postoperatively. Conclusions Daily drainage decreased following the theoretical decline of acute inflammation. In concordance with the literature, daily serum production may not be related to the use of ADM.