The use of skin-sparing mastectomy (SSM) with immediate reconstruction is preferred, as it has cosmetic and psychological advantages, and comprises one operation. We retrospectively reviewed the complication rate after SSM and immediate reconstruction with implants in 141 consecutive patients with 208 reconstructions. Risk factors were related to both patients and the procedure. The overall morbidity was 42/208 (20%) with one or more minor or major complications including epidermolysis, skin necrosis, or infection. The overall explantation rate was 26/208 (13%). Smoking was a significant risk factor for infection and explantation, and tended to increase risk of necrosis (p = 0.05). Preoperative radiation did not increase the risk of explantation. Age above the median of 44 (range 25-67) years implied a significantly increased risk of epidermolysis, infection, and explantation. Women who had a one-stage procedure with implantation of fixed-sized implant experienced explantation four times more often than women who had a two-stage procedure with tissue expander (p = 0.001). In conclusion, SSM with immediate reconstruction yields a low complication rate when patients are carefully selected. SSM with immediate reconstruction should be done for younger women who have had no previous radiation. Patients should stop smoking to ensure optimal outcome.