Background and objectives AKI is classified as prerenal, intrinsic, and postrenal. Prerenal AKI and intrinsic AKI represent the most common causes for AKI in hospitalized patients. This study aimed to examine the accuracy of the fractional excretion of sodium for distinguishing intrinsic from prerenal AKI. Design, setting, participants, & measurements We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, the Cochrane Library, and Scopus for all available studies that met the criteria until December 31, 2021. We included studies that evaluated fractional excretion of sodium in differentiating AKI etiologies in adults, whereas studies that did not have sufficient data to extract a 2×2 table were excluded. We assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and extracted the diagnostic accuracy data for all included studies. We conducted a meta-analysis using the bivariate random effects model. We performed subgroup analysis to investigate sources of heterogeneity and the effect of the relevant confounders on fractional excretion of sodium accuracy. Results We included 19 studies with 1287 patients. In a subset of 15 studies (872 patients) that used a threshold of 1%, the pooled sensitivity and specificity for differentiating intrinsic from prerenal AKI were 90% (95% confidence interval, 81% to 95%) and 82% (95% confidence interval, 70% to 90%), respectively. In a subgroup of six studies (511 patients) that included CKD or patients on diuretics, the pooled sensitivity and specificity were 83% (95% confidence interval, 64% to 93%) and 66% (95% confidence interval, 51% to 78%), respectively. In five studies with 238 patients on diuretics, the pooled sensitivity and specificity were 80% (95% confidence interval, 69% to 87%) and 54% (95% confidence interval, 31% to 75%), respectively. In eight studies with 264 oliguric patients with no history of CKD or diuretic therapy, the pooled sensitivity and specificity were 95% (95% confidence interval, 82% to 99%) and 91% (95% confidence interval, 83% to 95%), respectively. Conclusions Fractional excretion of sodium has a limited role for AKI differentiation in patients with a history of CKD or those on diuretic therapy. It is most valuable when oliguria is present.