Introduction. Total hip arthroplasty (THA) is a highly successful procedure achieving excellent clinical outcomes beyond 10 years post-surgery. With exception of periprosthetic infection, dislocation is the most common cause of failure in THA. A novel reverse total hip (RTH) replacement has been developed to address dislocation through reversal of the typical THA articulation in which a femoral cup and acetabular ball interlock at the extremes of motion to enhance mechanical stability in all planes. The purpose of this study was to assess the safety and efficacy of this novel RTH in a series of 22 patients and to monitor implant fixation using radiostereometric analysis (RSA). Methods. Twenty two patients with end-stage osteoarthritis of the hip were enrolled between 2017 and 2019 at a single center. All surgeries were performed by a group of four high-volume fellowship-trained arthroplasty surgeons. All patients received at least 1 acetabular cup screw and RSA markers inserted into the acetabulum and proximal femur. Follow-up time points were 6 weeks, 6, 12 and 24 months and included patient reported outcome measures (HOOS, Oxford-12, Harris Hip Score, SF-36 and Satisfaction) as well as RSA assessment. Results. The patient cohort consisted of 11 females and 11 males with mean age of 70.8 years and body mass index 31.3 kg/m. 2. At the time of writing, 21, 15 and 3 patients had completed their 6-month, 1- and 2-year clinical follow-ups, respectively. There was a significant improvement in function and pain with the RTH between pre-operative and six and twelve month follow up as collected by the HOOS, Oxfrod-12, HHS, WOMAC, EQ-5D and SF-36 PCS with p<0.001 for all. The sole exception was the SF-36 MCS which had a non-statistical improvement. Eighteen of 20 patients were satisfied or very satisfied with the outcome of surgery. Average vertical migration of the acetabular cup at 6 and 12 months was 0.082 mm and 0.110 mm, respectively. Average distal migration of the femoral stem at 6 and 12 months was 0.015 mm and 0.035 mm, respectively. Conclusions. Early results indicate acceptable safety and efficacy of this novel RTH for treating osteoarthritis of the hip. The femoral and acetabular components both appear well fixed at near-term follow-up, as assessed with RSA. Further follow-up will determine if these results are maintained at 24 months post-surgery. Additional patient enrollment will assess acetabular cup fixation without the use of screws. For any figures or tables, please contact authors directly