IMPORTANCE: An increasing number of patients with breast cancer receiving neoadjuvant chemotherapy (NACT) undergo immediate breast reconstruction (IBR) with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) as surgical treatment. However, the oncologic efficacy and safety of this treatment sequencing strategy is unclear. OBJECTIVE: To compare the long-term oncologic outcomes of IBR with NSM/SSM and conventional mastectomy (CM) alone for breast cancer in the NACT setting. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, propensity score–matched case-control study was conducted at Asan Medical Center, Seoul, Korea. A total of 1266 patients with breast cancer who underwent NACT followed by mastectomy with or without breast reconstruction between January 1, 2010, and November 30, 2016, were included. Data analysis was performed from July 1, 2019, to January 24, 2020. After propensity score matching, 323 patients who underwent IBR with NSM/SSM and 323 who underwent CM alone were selected for comparison of long-term oncologic outcomes. MAIN OUTCOMES AND MEASURES: The 5-year local recurrence–free survival, disease-free survival, distant metastasis–free survival, and overall survival rates were calculated using the Kaplan-Meier method and compared using log-rank tests. Hazard ratios (HRs) and 95% CIs were estimated using the Cox proportional hazards regression model. RESULTS: After matching, the median follow-up periods were 67 (range, 17-125) months for the IBR group and 68 (range, 17-126) months for the CM-alone group. Median age of the women in the IBR group was 42 (range, 23-72) years; median age of those in the CM-alone group was 46 (range, 30-75) years. No significant differences were observed between the IBR and CM-alone groups in local recurrence (3.7% vs 3.4%; P = .83), regional recurrence (7.1% vs 5.3%; P = .33), or distant metastasis (17.3% vs 18.6%; P = .68) rates. There was also no significant difference between the IBR and CM-alone groups in 5-year local recurrence–free survival (95.6% vs 96.7%; HR, 1.124; 95% CI, 0.495-2.549; P = .78), disease-free survival (76.5% vs 79.9%; HR, 1.089; 95% CI, 0.790-1.500; P = .60), distant metastasis–free survival (82.5% vs 82.5%; HR, 0.941; 95% CI, 0.654-1.355; P = .74), or overall survival (92.0% vs 89.3%; HR, 0.847; 95% CI, 0.530-1.353; P = .49) rates. CONCLUSIONS AND RELEVANCE: The long-term oncologic outcomes of IBR with NSM/SSM for breast cancer in this study appeared to be comparable to those of CM alone after NACT, suggesting the feasibility of IBR with NSM/SSM in the NACT setting.