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Background: The increasing use of autologous fat grafting (AFG) in breast cancer patients has raised concerns regarding its potential to obscure radiographic monitoring and precipitate cancer recurrence. Given the paucity of strong data addressing these concerns, this study evaluates patient outcomes and tumor recurrence following oncologic resection and AFG. Methods: Retrospective chart review identified patients who underwent oncologic resection for breast cancer or carcinoma in situ, followed by breast reconstruction, from 2010 to 2015. 524 patients met inclusion criteria: 148 (28.2%) patients underwent AFG, while 376 (71.7%) patients did not (control group). Patient demographics, cancer characteristics, oncologic treatment, surgical treatment, and outcomes were analyzed. Results: Patients in the AFG and control groups had similar BMIs, smoking statuses, and BRCA statuses. Patients who underwent AFG were significantly younger (47.6 vs. 52.1 years, p<0.05), and were less likely to have diabetes (2% vs. 7.2%, p<0.05). In per breast analysis, the two groups demonstrated similar therapeutic vs. prophylactic indication rates, distribution of Stage 1, 2, and 3 cancer, and rates of chemotherapy and radiation. DCIS was more common in the AFG group (20.6% vs. 14.5%, p=0.013), while hormone therapy was less common (52.4% vs. 67.5%, p=0.012). Each breast underwent 1 to 4 AFG procedures: 1 in 83.1%, 2 in 13.7%, 3 in 2.8%, and 4 in 0.4%. Mean follow-up time from initial surgery was 42.1 and 34.5 months in the AFG and control groups (p<0.01). There were no significant differences in overall complication rates following initial reconstruction (pre-AFG) (AFG 25.2% vs. control 23.5%), or in rates of infection, wound healing complications, hematoma, seroma, implant exposure, and flap failure. The overall complication rate following AFG was 9.4%; with 1.7% infection, 1.3% fat necrosis, 6.0% oil cyst, and 0.4% wound healing problem rates. There were no incidences of seroma or hematoma following AFG. Among breasts receiving surgery for therapeutic indications (AFG n=162, control n=414), there were similar rates of local recurrence: AFG 2.5%, control 1.9% (p=0.688). Interestingly, mean time to recurrence was significantly longer in the AFG group (52.3 vs. 22.8 months from initial surgery, p=0.02). Conclusions: AFG is a powerful tool in breast reconstruction. This large single-institution study, which evaluates patients of comparable BRCA status, cancer staging, chemotherapy, and radiation therapy, provides valuable evidence-based support for its oncologic safety.