In this study, the effects of procedure type, timing, and other clinical variables on complication rates in mastectomy reconstruction were prospectively evaluated. Using a prospective cohort design, women undergoing first-time, immediate or delayed breast reconstruction were recruited from 12 centers and 23 plastic surgeons. Complication data for expander/implant, pedicle transverse rectus abdominis musculocutaneous (TRAM) flap, and free TRAM flap procedures were evaluated 2 years after surgery in 326 patients. For each patient, the total number of complications was recorded and the complication data were dichotomized in two ways: (1) total complications and (2) major complications (those requiring reoperation, rehospitalization, or nonperioperative intravenous antibiotic treatment). The effects of procedure type, timing, radiotherapy, chemotherapy, age, smoking, and body mass index on complication rates were analyzed using logistic regression. Immediate reconstructions had significantly higher total as well as major complication rates, compared with delayed procedures (p = 0.011 and 0.005, respectively). Furthermore, higher body mass indexes were associated with significantly higher total and major complication rates (p = 0.005 and p < 0.001, respectively). No significant effects on complication rates were noted for procedure type or for the other independent variables, although there was evidence of trends for higher total and major complication rates in implant patients who received radiotherapy and a trend for higher major complication rates in TRAM flap patients who received chemotherapy. It was concluded that (1) immediate reconstructions were associated with significantly higher complication rates than delayed procedures, and (2) procedure type had no significant effect on complication rates.