To determine the quality of life (QoL) of breast cancer patients who underwent mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap (LD), and the oncological safety of the procedure. Between May 2001 and March 2007, 2,566 patients had breast cancer surgery at the National Cancer Center, Korea. Of the 2,566 patients, 1,699 had breast-conserving surgery (BCS) and 120 had a mastectomy with an immediate LD. We retrospectively compared the oncologic safety of the two techniques. We also assessed the QoL using the EORTC QLQ BR-23 and Zung's self-rating depression scale in 52 LD patients, 104 age- and stage-matched patients who underwent BCS, and 104 age-matched healthy women. The LD group had earlier stage disease than the BCS group at baseline, but following surgery, the groups did not differ in the rates of local recurrence or systemic metastases. Compared with the healthy group, the patient groups had poorer functioning and more depression (p < 0.001). Among the patient groups, the LD group reported lower scores for body image (p = 0.007) and future perspective (p = 0.023) than the BCS group. In the LD group, patients who received neoadjuvant chemotherapy reported lower scores for future perspective and higher scores for depression than those who did not receive neoadjuvant chemotherapy (p < 0.001). The BCS and LD groups did not differ in oncological outcome, and the QoL of patients in the LD group was not always good. Mastectomy with immediate reconstruction should be considered carefully and tailored to the patient's needs and characteristics.