Abstract The objective of this study was to conduct a systematic review and meta-analysis of relevant randomized control trials (RCTs) to determine the role of ibuprofen, as well as the optimum dose and duration of therapy, in preventing the incidence of heterotopic ossification (HO) after primary total hip arthroplasty (THA). A literature search was performed using the PubMed/MEDLINE and Cochrane Library databases for RCTs that compared the use of ibuprofen versus placebo as prophylaxis for HO in patients after THA. The main outcomes for this study were overall occurrence of HO, occurrence according to the Brooker classification, and gastrointestinal complications. A total of 27 potential articles were identified from the database. Eventually, four trials with 1,153 patients were included in the final analysis. When compared with placebo, the use of ibuprofen is associated with a reduction in the incidence of HO at the 3- and 12-month follow-up appointments, as well as the incidence of Brooker II and III HO (p < 0.05). However, there was no significant difference between the ibuprofen and placebo groups in terms of treatment discontinuation due to gastrointestinal complications or the incidence of Brooker I and IV HO (p > 0.05). The existing data indicates that ibuprofen is safe and efficacious in reducing the total incidence of HO along with Brooker II and III HO at follow-up. However, due to the small number of studies, the conclusions are limited; therefore, more high-quality clinical trials are required to develop guidelines for optimal dose and duration of therapy.