OBJECTIVE The National Healthcare Safety Network classifies breast operations as clean procedures with an expected 1%-2% surgical site infection (SSI) incidence. We assessed differences in SSI incidence following mastectomy with and without immediate reconstruction in a large, geographically diverse population. DESIGN Retrospective cohort study PATIENTS Commercially insured women aged 18-64 years with ICD-9-CM procedure or CPT-4 codes for mastectomy from January 1, 2004 through December 31, 2011 METHODS Incident SSIs within 180 days after surgery were identified by ICD-9-CM diagnosis codes. The incidences of SSI after mastectomy with and without immediate reconstruction were compared using the χ2 test. RESULTS From 2004 to 2011, 18,696 mastectomy procedures among 18,085 women were identified, with immediate reconstruction in 10,836 procedures (58%). The incidence of SSI within 180 days following mastectomy with or without reconstruction was 8.1% (1,520 of 18,696). In total, 49% of SSIs were identified within 30 days post-mastectomy, 24.5% were identified 31-60 days post-mastectomy, 10.5% were identified 61-90 days post-mastectomy, and 15.7% were identified 91-180 days post-mastectomy. The incidences of SSI were 5.0% (395 of 7,860) after mastectomy only, 10.3% (848 of 8,217) after mastectomy plus implant, 10.7% (207 of 1,942) after mastectomy plus flap, and 10.3% (70 of 677) after mastectomy plus flap and implant (P<.001). The SSI risk was higher after bilateral compared with unilateral mastectomy with immediate reconstruction (11.4% vs 9.4%, P=.001) than without (6.1% vs 4.7%, P=.021) immediate reconstruction. CONCLUSIONS SSI incidence was twice that after mastectomy with immediate reconstruction than after mastectomy alone. Only 49% of SSIs were coded within 30 days after operation. Our results suggest that stratification by procedure type facilitates comparison of SSI rates after breast operations between facilities.