ABSTRACT Objective To compare the effects of continuous combined conjugated equine estrogens (CEE) with those of tibolone on symptom control, lipid profile, and tolerability in women with surgical menopause. Materials and methods This was a randomized controlled trial study conducted in the Department of Obstetrics and Gynaecology of Global Rainbow Hospital Pvt. Ltd., Agra (2014–2016) comprising 150 women. Generally, healthy postmenopausal women having undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy irrespective of age and indication of surgery and no absolute contraindications to hormone replacement therapy (HRT) or tibolone were enrolled. Fifty subjects did not receive any HRT, 50 were treated with CEE 0.625 mg, and 50 were given tibolone 2.5 mg for 13 treatment cycles, each of 28 days. Results were statistically analyzed regarding drug efficacy in amelioration of menopausal symptoms and side effects at follow-up periods of 1, 6, and 12 months. Results A total of 150 subjects were enrolled and received at least one dose of the study medication, of which 134 (89.4%) subjects completed the study (n = 40 in CEE and n = 44 in tibolone). The incidence of postmenopausal symptoms decreased significantly over time in the treatment groups, compared with baseline, including significant decreases in the incidence of urogenital and sexual health symptoms, with p-values 0.001 and 0.004 in cases that received CEE and tibolone respectively. Significant differences in symptom control (other than hot flashes) were observed between treatment groups in a few different cycles for different symptoms, but no consistent or clinically significant trends were observed. Significant decreases in total cholesterol (5.6%) and low-density lipoprotein cholesterol (7.5%) were observed at cycle 13, compared with baseline, in the CEE group, and significant decreases in high-density lipoprotein cholesterol (8.5%) and triglycerides (13.7%) were observed at cycle 13, compared with baseline, in the tibolone group. Significant weight gain was observed at cycle 13 in the tibolone group (3.05 kg), compared with the CEE group (0.96 kg). The incidences of adverse events were similar in both treatment groups. Conclusion Women treated with CEE and tibolone showed significant improvement of climacteric symptoms, including urogenital and sexual health symptoms. Treatment with either preparation significantly improved subjective wellbeing, vasomotor symptoms, and vaginal dryness. The CEE and tibolone each induced a different mix of beneficial changes in the lipid profile. It is seen that tibolone seems to be effective on estrogen withdrawal symptoms and with its acceptable androgenic side effects can be an appropriate selection for HRT in postmenopausal women with decreased sexual desire. How to cite this article Gupta N. Hormone Replacement Therapy for Surgical Menopause: Is there an Ideal Drug? A Comparative Study of Conjugated Equine Estrogens and Tibolone. J South Asian Feder Menopause Soc 2017;5(1):11-15.