Abstract Background The definition of an adequate surgical margin for breast cancer has been a hotly debated topic for over 20 years, with “no ink on tumor” now widely recognized as an adequate pathological margin for invasive carcinoma. Patients with dense breasts pose unique challenges in terms of accurate pre-operative evaluation of extent of disease and achieving adequate margins at initial surgery. The aim of this study therefore is to analyze re-excision rates and correlate with breast density and other clinical and pathological factors before and after the decision to accept 'no tumor at the inked margin” as an adequate margin. Methods Patients with stage I or II invasive breast cancer treated with breast conserving surgery between the 1st of June 2013 and the 31st of October 2014 were included. Patients who had surgery prior to January 1, 2014 comprise the pre-guideline group whereas those who had surgery on or after January 1, 2014 comprise the post-guideline group. Breast density was assessed by 2 independent radiologists. Inter-reader agreement was assessed using data on all study subjects and intra-reader agreement was assessed on a random sample of 121 study subjects; agreement was assessed using the kappa statistic with bootstrap confidence intervals. Logistic regression was used to model the association between breast density and re-excision, using the minimum value of breast density according to the two independent readers, within the 2 time periods. Multivariable logistic regression adjusted for patient and disease characteristics associated with re-excision on univariable analysis. Results The inter-reader agreement was 0.633 (95% confidence interval (CI): 0.604, 0.663) whereas the intra-reader agreement was 0.755 (95% CI: 0.663, 0.834). A total of 1205 patients were included, of whom 504 (41.8%) had surgery before the guideline change and 701 (58.2%) after. Overall 214 (17.8%) had at least one re-excision. The re-excision rate was significantly lower in the time period after the guideline change (15.1% verus 21.4%, p=0.006). There was no significant difference in tumor characteristics between the time periods. Younger age at diagnosis was the only clinicopathological factor that was significantly associated with increased breast density (p<0.001). On univariable analysis, increased breast density was associated with higher risk of re-excision (p=0.005), as was younger age, multifocality, presence of DCIS, HER2 status and extensive intraductal component (EIC). On multivariable analysis, time period, age at diagnosis, multifocality, presence of DCIS and EIC were significantly associated with re-excision, but breast density was not (OR 1.24, 95% CI 0.98-1.56, p=0.07). Conclusions Women who are of younger age at diagnosis are more likely to have increased breast density. Although, younger age was associated with higher rate of re-excision, we did not find breast density to be associated with a higher rate of re-excision on multivariable analysis. Citation Format: Walsh SM, Brennan SB, Zabor E, Rosenberger LH, Stempel M, Lebron-Zapata L, Gemignani ML. Does breast density increase the risk of re-excision for women with breast cancer having breast conservation therapy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-10.