BACKGROUND:A closed-suction drain is usually inserted during tissue expander–based breast reconstruction. Prolonged duration of drain retention can disturb patients’ daily lives and affect overall sociomedical costs. This study aimed to investigate factors that may influence the drainage and to identify predictors of unusually prolonged drain duration. METHODS:Patients who underwent delayed-immediate, two-stage breast reconstruction using a tissue expander between January of 2013 and July of 2017 were reviewed. Prolonged drain duration was defined as drain duration for longer than the 75th percentile of that for the entire cohort. Effects of patient- and operation-related variables on drainage and prolonged drain duration were evaluated. RESULTS:A total of 1056 cases (1002 patients) were analyzed. The median drain duration was 10 days. Drain placement for more than 12 postoperative days was observed in 256 cases (24.2 percent), classified as prolonged drain duration. Multivariate analyses demonstrated that old age, high body mass index, neoadjuvant chemotherapy, insertion of large Siltex textured tissue expanders, and greater volume of initial inflation were independent risk factors of prolonged drain duration. The size and texture of the tissue expanders and initial inflation volume retained their influence, regardless of mastectomy specimen weight. Use of acellular dermal matrix had contradictory effects according to breast size, being protective against prolonged drain duration in cases with mastectomy specimen weight greater than 400 g, and being a significant predictor for it in cases with mastectomy specimen weight less than or equal to 400 g. CONCLUSION:Several factors, including reconstructive operation-related factors, might influence drain duration following tissue expander–based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, III.