Prepectoral implant-based breast reconstruction is often supplemented by autologous fat grafting to optimize aesthetic outcomes. This usually entails several rounds of modest fat transfer to minimize risk of necrosis; however, the limits of fat grafting at expander exchange are not known. A single-institution retrospective review from July 2016 to February 2022 was performed of all patients who underwent (1) mastectomy, (2) prepectoral tissue expander placement, (3) expander exchange for implant, and (4) at least one round of autologous fat transfer. Student t test and χ 2 test were used. A total of 82 breasts underwent a single round of fat grafting during implant placement (group 1); 75 breasts underwent fat grafting that occurred in multiple rounds and/or in delay to implant placement (group 2). Group 1 received more fat at the time of implant placement (100 mL; interquartile range, 55-140 mL; P < 0.001) and underwent fewer planned operative procedures compared with group 2 (1.0 vs 2.2, P < 0.001). Total fat volume in group 2 did not significantly exceed that of group 1 until after 3 rounds of fat transfer (128.5 mL; interquartile range, 90-130 mL; P < 0.01). There was no difference in the rate of fat necrosis between groups after the first round (15.9% vs 9.3%, P = 0.2) and final round (15.9% vs 12.0%, P = 0.5) of fat grafting. Complication rates were similar between groups (3.7% vs 8.0%, P = 0.2). A 2-stage approach of prepectoral tissue expander placement with single round of larger volume fat transfer at expander exchange reduces overall number of operative procedures without increased risks.