BACKGROUND: Numerous risk factors for the complications of two-stage, immediate implant-based breast reconstruction have been identified, although few studies have directly examined the impact of breast size and expansion protocols on the surgical outcomes of breast reconstruction. This study aimed to evaluate the impact of breast size, expansion velocity, and volume-related variables on postoperative complications of breast reconstruction. METHODS: The cohort involved patients who underwent immediate breast expander reconstruction at a single center between 2017 and 2019. The breast size was classified into three categories according to the weight of the mastectomy specimen as small (<300 g), medium (>/=300 g, 500 g). Multifactorial logistic regressions were used to assess the impact of variables, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for predicting the complication event. RESULTS: Of the 174 breasts (168 patients), 51 (29.3%), 66 (37.9%), and 57 (32.6%) breasts were classified as small, medium, and large, respectively. The rate of infection (P=0.014) and expander/implant failure (P=0.007) significantly differed according to breast size, with the rate being the highest in large breasts. Multivariate logistic regression analysis showed that body mass index (BMI) [odds ratio (OR): 1.25; P=0.003], nipple-sparing mastectomy (OR: 2.82; P=0.036), sentinel biopsy (OR: 5.10; P=0.016), final expansion volume (OR: 0.99; P=0.022), and expansion velocity (OR: 0.703; P=0.024) were significant independent predictors of any complication. In the ROC analysis, breast weight >696 g could predict the possibility of revision surgery, with a sensitivity of 42.9% and specificity of 81.8%. CONCLUSIONS: The final expansion volume and expansion velocity have a significant negative relationship with overall complications in breast reconstruction. A standard expansion protocol needs to be established to ensure the success of two-stage breast reconstruction.