Background Closed-suction drains are widely used in expander-based breast reconstruction. These drains are typically removed using a volume-based criterion. The drainage volume affects the hospital stay length and the recovery time. However, few studies have analyzed the factors that influence drainage volume after expander-based breast reconstruction. Methods We retrospectively analyzed data regarding daily drainage from patients who underwent expander-based breast reconstruction between April 2014 and January 2018 (159 patients, 176 expanders). Patient and operative factors were analyzed regarding their influence on total drainage volume and drain placement duration using univariate and multivariate analyses and analysis of variance. Results The mean total drainage volume was 1,210.77±611.44 mL. Univariate analysis showed correlations between total drainage volume and age (B=19.825, P<0.001), body weight (B=17.758, P<0.001), body mass index (B=51.817, P<0.001), and specimen weight (B=1.590, P<0.001). Diabetes history (P<0.001), expander type (P<0.001), and the surgical instrument used (P<0.001) also strongly influenced total drainage. The acellular dermal matrix type used did not affect total drainage (P=0.626). In the multivariate analysis, age (B=11.907, P=0.004), specimen weight (B=0.927, P<0.001), and expander type (B=593.728, P<0.001) were significant predictors of total drainage. Conclusions Our findings suggest that the total drainage and the duration of drain placement needed after expander-based breast reconstruction can be predicted using preoperative and intraoperative data. Patient age, specimen weight, and expander type are important predictors of drainage volume. Older patients, heavier specimens, and use of the Mentor rather than the Allergan expander corresponded to a greater total drainage volume and a longer duration of drain placement.