The study aimed to assess the safety of one-stage bilateral total hip arthroplasty (THA) compared with unilateral THA. In this retrospective observational case-control study were included patients undergoing unilateral (group 1) and one-stage bilateral (group 2) THA in a high-volume center. The groups were matched for gender, age at surgery, and pre-operative American Society of Anesthesiology score. The following variables were assessed: local and systemic complications, postoperative anemia, 30-day and 1-year readmission and reoperation rates, length of hospital stay, and ambulation time. Group 1 reported a significantly higher rate of local and systemic complications compared with group 2 (5.4% versus 3.9% and 29.6% versus 4.7%, respectively). Postoperative anemia was significantly lower in group 1 compared with group 2 (8.1% versus 30%). There was no significant difference in terms of 30-day and 1-year readmission rates between the two groups. The average length of hospital stay was 5.1 ± 2.3 days in group 1, and 5.3 ± 1.9 days in group 2 (p = 0.78). Ambulation time was significantly lower for group 1 (day 0.9 ± 0.9 in group 1, and day 1 ± 0.8 in group 2, p = 0.03). In a high-volume center, one-stage bilateral THA is a safe procedure compared with unilateral THA in terms of postoperative local and systemic complications, 30-day readmission and 1-year reoperation rates, and length of hospital stay.