Background: Nipple-sparing mastectomy (NSM) is a technically feasible and oncologically sound option for patients who meet eligibility criteria. Inframammary fold (IMF) incision results in a well-hidden scar and enhanced final aesthetic result. While oncologic eligibility criteria have been well established, reconstructive criteria are less defined. We report Moffitt Cancer Center's (MCC) outcomes with IMF incision for NSM and immediate reconstruction, and factors associated with increased complication rate.Methods: IRB approved retrospective cohort study of patients who underwent NSM through an IMF approach with immediate reconstruction at MCC from 2006-2013 was conducted. Analysis included patient demographics, tumor characteristics, ancillary treatment, reconstructive method, and nipple and skin flap necrosis. A literature review was performed to compare outcomes with other types of incisions.Results: 115 patients met inclusion criteria, representing 199 breasts. The average age was 48.1 (range 18-74). The two main complication categories evaluated were nipple necrosis (8%) and skin flap necrosis (10.6%). Older age demonstrated a significant relationship with skin flap necrosis (p=0.0155) and overall complications (p=0.0492). Complication rate was significantly higher in the cancer side vs. prophylactic side in patients who underwent bilateral mastectomies (p=0.0088). Factors with trends related to increased skin flap necrosis included increased mastectomy specimen weight (p=0.0704), smoking (p=0.0726), and significant comorbidities (p=0.0665).Conclusion: Our institution's results substantiate that NSM through an IMF approach with immediate reconstruction is a viable option. Recognized risk factors such as age, laterality, breast weight, smoking history, and comorbidities associated with increased complications should be considered when determining patient selection for reconstruction.