Purpose: To evaluate the clinical performance of tomosynthesis guided vacuum assisted breast biopsy (TVAB) and compare it to conventional stereotactic vacuum assisted biopsy (SVAB). Materials and Methods: From June 2013 to May 2017, all women who underwent breast biopsy were included in this retrospective study. Between June 2013 and April 2015, lesions were biopsied with SVAB. Since June 2015, all biopsies were performed with DVAB. Patient demographics, rates of aborted procedures, causes of abortions, as well as the radiologic and pathologic properties of lesions were compared between these two groups. The significance level was accepted as p<0.05. Results: From June 2013 to May 2017, 336 patients with 352 lesions (mean age 56.05±10.54) underwent SVAB and 516 patients with 555 lesions (mean age 56.05±10.27) underwent DVAB. 5.4% of SVAB and 4.1% of DVAB were cancelled due to non-visualization or difficult lesion location. Eight patients underwent DVAB had self-limiting vasovagal reaction; none reported in SVAB group. The rates of high-contrast lesions with calcifications were 83% in SVAB and 74% in DVAB while the rates of low-contrast lesions without calcifications were 17% and 26% in SVAB and DVAB, respectively (p=0.002). No statistically significant differences were found between the two groups with respect to histological results of lesions (p=0.074). Invasive breast cancers mostly presented as low contrast lesions while ductal carcinoma in situ (DCIS) as high contrast lesions (p<0.001). Conclusion: DVAB has a better clinical performance compared to SVAB because it can successfully biopsy not only the high contrast lesions detected on mammography but also the low contrast lesions only visualized on tomosynthesis. While high contrast lesions have more DCIS, low contrast lesions are often associated with a high rate of invasive breast cancer. DVAB can replace SVAB in routine clinic practice but at a cost of low rate of vasovagal reaction.