Objective To examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA). Methods Between January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer-generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm(2)with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%. Results A total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (allP> 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (bothP< 0.05); there were significant differences in Gruen zones 1, 4, 6, and 7 at 12 months postoperatively (allP< 0.01); there were significant differences in Gruen zones 1, 2, 4, 6, and 7 at 24 months postoperatively (allP< 0.001). Patients taking raloxifene reported higher QoL scores, with better improvement in BMD in all areas except in zones 3 and 5 compared with the control group. There were no significant differences in WOMAC pain (P= 0.4045), WOMAC function (P= 0.4456) and women's QoL scores (P= 0.5983) between groups before surgery. However, WOMAC pain, WOMAC function and women's QoL score in the treatment group were significantly better at all time points (allP< 0.05). Patients in the treatment group showed no increased adverse events, including cardiac events, stroke, venous thromboembolism, and gynecological cancer (allP> 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P= 0.0437). Conclusion Raloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.