BACKGROUND: There is limited evidence available in the literature with regard to the complication profile of mastectomy and immediate prosthetic reconstruction in augmented patients. OBJECTIVES: The aim of this systematic review and meta-analysis was to compare postoperative complications between women with vs without prior augmentation undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction. METHODS: A systematic search was conducted in February 2020 for studies comparing women with vs without prior augmentation undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction with documentation of postoperative complications. Outcomes analyzed included early, late, and overall complications. Pooled odds ratios (ORs) with 95% CIs were obtained through meta-analysis. RESULTS: Our meta-analysis, which included 6 studies comparing 241 breasts with prior augmentation and 1441 without, demonstrated no significant difference between the 2 groups in rates of early (36.7% vs 24.8%: OR, 1.57; 95% CI, 0.94-2.64; P = 0.09), late (10.1% vs 19.9%: OR, 0.53; 95% CI, 0.06-4.89; P = 0.57), and overall complications (36.5% vs 31.2%: OR, 1.23; 95% CI, 0.76-2.00; P = 0.40). Subgroup analysis showed a significantly higher rate of hematoma formation in the augmented group (3.39% vs 2.15%: OR, 2.68; 95% CI, 1.00-7.16; P = 0.05), but no difference in rates of seroma, infection, mastectomy skin flap necrosis, and prosthesis loss. CONCLUSIONS: Our meta-analysis suggests that prior augmentation does not significantly increase overall postoperative complications in women undergoing skin- or nipple-sparing mastectomy and immediate prosthetic reconstruction. However, the significantly higher rate of hematoma formation in augmented patients warrants further investigation and preoperative discussion.