Background The intra-individual difference in cystatin C–based and creatinine-based estimated glomerular filtration rate (eGFRcys and eGFRcr, respectively), i.e. eGFR discordance, has recently been demonstrated to have prognostic implications. eGFR discordance was associated with mortality, cardiovascular and renal outcomes. We present a systematic review and meta-analysis to summarize the existing literature. Methods We searched PubMed, Embase and MEDLINE up to 28 April 2024 for cohort and cross-sectional studies in English reporting the association of eGFR discordance with mortality, cardiovascular and renal outcomes. The quality of studies was evaluated by Risk Of Bias In Non-randomized Studies—of Exposure (ROBINS-E) form. Data from studies were extracted to a pre-defined table and pooled using a random-effects model. Stratified and sensitivity analyses were performed. Results A total of 1489 studies were initially identified, of which 18 studies with longitudinal or cross-sectional designs were included, with a sample size between 373 and 363 494 people. In general, the risk of bias was graded as “low“ or “some concerns”. eGFR was mainly calculated using Chronic Kidney Disease Epidemiology Collaboration equations, while a few studies applied other equations. An eGFR discordance featuring lower eGFRcys, e.g. eGFRcys ≤60% of eGFRcr, or eGFRcys-eGFRcr ≤–15 mL/min/1.73 m2, was consistently associated with higher mortality and elevated risk of cardiovascular and renal outcomes. People with lower eGFRcys have a 58% greater risk of mortality [hazard ratio (HR) = 1.58, 95% confidence interval (CI) 1.42, 1.76] and 32% greater risk of cardiovascular events (HR = 1.32, 95% CI 1.25, 1.39). People with higher eGFRcys have a 39% lower risk of mortality (HR = 0.61, 95% CI 0.52, 0.70) and 29% lower risk of cardiovascular events (HR = 0.71, 95% CI 0.62, 0.81). No meta-analysis for renal outcomes was conducted due to data availability. Conclusions The eGFR discordance serves as a meaningful indicator of adverse health outcomes. The lack of a consensus on the cut-off value of eGFR discordance and the mixture use of eGFR equations warrants attention.