BACKGROUND: Patient-reported outcomes are of ever-increasing importance in medical decision-making. The EQ-5D is one of the generic instruments measuring health-related quality of life (HRQoL) in arthroplasty. This review aimed to identify possible predictors of HRQoL changes for patients undergoing total knee replacements (TKR) or total hip replacements (THR). METHODS: A systematic literature review according to the PRISMA guidelines was conducted, searching several databases. Preoperative to postoperative HRQoL changes were evaluated in patients undergoing THR or TKR, using the EQ-5D visual analog scale (VAS) or the preference-based EQ-5D Index were evaluated. Articles were considered with prospectively or retrospectively collected data, as well as registry data, each with statistical analyses of patient-related factors. RESULTS: Eight hundred eighty-two articles were found, of which 21 studies met the inclusion criteria. Predictors were distinguished in alterable and non-alterable ones. The EQ-5D Index indicated a tendency towards beneficial improvements for patients with a high body mass index (BMI) (> 40) and no significant results for the VAS. Additionally, one study found that patient education and preoperative physiotherapy appeared to enhance HRQoL. Some evidence indicated that male gender was negatively associated with changes in the VAS and the EQ-5D Index, but one study reported the opposite. Changes in VAS and EQ-5D Index were lower for older patients, whereas a higher educational level seemed to be advantageous. A high Charnley class led to deteriorating changes in VAS, although a high Kellgren Lawrence classification was positively associated with the EQ-5D Index, in a limited number of studies. For all results, clinical relevance was calculated differently and mainly reported as uncertain or small. CONCLUSIONS: The literature on this topic was weak and offers only limited guidance. Results for alterable predictors, such as the BMI, indicated valuable improvements for highly obese patients. Further, high-quality research is required to support medical decision-making. LEVEL OF EVIDENCE: Level IV, according to the OCEBM Levels of Evidence Working Group.