Background: Roughly 80% of patients undergoing mastectomy in the United States opt for reconstruction with implants. The introduction of acellular dermal matrices has allowed for placement of breast prostheses in the prepectoral plane, while a new carbon dioxide tissue expander (TE) (AeroForm) allows for needle-free, patient-controlled expansion. These 2 novel technologies have ushered in a new patient-centered era of breast reconstruction, with the possibility of reducing patient morbidity for the first time in decades. We hypothesize that AeroForm expanders placed in the prepectoral plane reduce time to second-stage reconstruction, reduce the number of clinic visits, and have lower complications than traditional saline TEs. Methods: This is a retrospective review of all patients undergoing breast mastectomy and TE placement in the prepectoral plane over a 21-month period (169 patients, 267 breasts), comparing AeroForm expanders to TEs. Results: The AeroForm group (n = 57) had a shorter period to second-stage reconstruction than the TE group (n = 210) (135.4 versus 181.7 days; P = 0.01) and required fewer clinic visits (5.1 versus 6.9; P < 0.01). Partial thickness (25.6% versus 12.3%, P = 0.03) and full thickness (8.7% versus 0.0%, P = 0.02) necrosis were more common in the saline cohort. The rates of infection, hematoma, and seroma requiring drainage were not statistically significant between the 2 groups. Conclusions: Two-staged breast reconstruction with the use of AeroForm expanders in the prepectoral space marks progress in improving care for breast cancer patients by demonstrating a reduction in some adverse events, the number of clinic visits, and the time to second-stage reconstruction.