Introduction Complications associated with the application of the Reamer–irrigator–Aspirator (RIA) system are described in the literature. However, to date a systematic review and meta-analysis to assess prevalence of complications associated with the use of the RIA system have not been conducted. Materials and methods The review is registered with PROSPERO (CRD42021269982). MEDLINE, the Web of Science Core Collection, and Embase were searched from the inception to 10 August 2021. The primary objective was to assess complications and blood loss associated with the use of the RIA system. Results Forty-seven studies involving 1834 procedures performed with the RIA system were finally included. A total of 105 complications were reported, with a pooled estimated overall prevalence of 1.7% with a 95% confidence interval (CI) of 0.40 to 3.60, with cortex perforation being the largest reported complication with a total of 34 incidences. A significant subgroup difference was observed (p = 0.02). In subgroup 1 (bone graft harvesting), complication prevalence was 1.4% (95% CI 0.2–3.4); in subgroup 2 (clearance intramedullary canal) it was 0.7% (95% CI 0.00–6.30) and in subgroup 3 (reaming with RIA system prior to nail fixation) 11.9% (95% CI 1.80–26.40). No statistically significant difference for tibia and femur as RIA system application site was observed (CI 0.69–4.19). In studies reporting blood loss, a mean volume of 803.29 ml, a mean drop of hemoglobin of 3.74 g/dl and a necessity of blood transfusion in 9.72% of the patients were observed. Conclusions The systematic review and meta-analysis demonstrate a low overall prevalence rate of complications associated with the RIA system. However, especially the risk of cortical perforation and the frequently reported relevant intraoperative blood loss are complications that should be anticipated in perioperative management and ultimately considered when using the RIA system.