Background: Sterile ready-to-use acellular dermal matrix, introduced as an alternative to aseptic freeze-dried acellular dermal matrix for implant-based breast reconstruction, has been investigated in a limited number of studies. This study compared outcomes in implant-based breast reconstruction with ready-to-use and freeze-dried acellular dermal matrix. Methods: The authors analyzed patients undergoing implant-based breast reconstruction with either freeze-dried or ready-to-use acellular dermal matrix, including demographics, clinical variables, and outcomes. An a priori power analysis was performed and logistic regression modeling was used to quantify the effect of acellular dermal matrix on outcomes while controlling for potential confounders. Results: A total of 1285 consecutive patients undergoing 2039 immediate prosthetic breast reconstructions constituted the population: 612 (n = 910 breasts) with freeze-dried matrix and 673 (n = 1129 breasts) with ready-to-use acellular dermal matrix. The freeze-dried matrix cohort had a significantly higher rate of explantation compared with the ready-to-use matrix cohort (18.0 percent versus 12.0 percent; p = 0.0036), but surgical-site infection, wound dehiscence, mastectomy flap necrosis, seroma, and hematoma did not differ significantly between groups. On multivariate regression, patients undergoing reconstruction with freeze-dried matrix, compared to ready-to-use matrix, did not have higher odds of experiencing surgical-site infections (OR, 1.064; p = 0.7455), but did have higher odds of explantation (OR, 1.570; p = 0.0161). Tobacco use (OR, 2.809; p = 0.0002) and body mass index (OR, 1.054; p < 0.0001) were also independent predictors of explantation. Conclusion: Immediate implant-based breast reconstruction with sterile ready-to-use acellular dermal matrix has a comparable overall safety profile and a lower rate of prosthetic explantations compared with aseptic freeze-dried acellular dermal matrix.