Background/Aims: To evaluate the feasibility and safety of single-port access total laparoscopic hysterectomy (SPA-TLH) for large uterus (>500 g). Methods: A prospective data collection was performed in 21 consecutive patients in March 2010 and August 2011. Surgical outcome including operative time (OT) and estimated blood loss (EBL) were analyzed. Results: SPA-TLH procedures were successfully performed in 16 cases (76.2%). Of the 5 failed cases, 4 were converted to multiport TLH because of distorted uterine contours and pelvic adhesions and 1 was converted to laparotomy for bleeding control. The median OT, uterine weight, and EBL were 110 (65–165) min, 600 (502–980) g, and 200 (100–800) ml, respectively. Spearman’s correlation analysis demonstrated that OT and blood loss increased with increasing uterine weight (p = 0.003 and p = 0.033, respectively). No operative complications were observed during the hospital stay and 3-month follow-up following discharge. Conclusion: SPA-TLH for large uterus is a feasible and safe technique.