Objective To evaluate whether goal-directed fluid therapy (GDFT) reduces the risk of renal injury in critical illness. Methods MEDLINE via PubMed, EMBASE, CENTRAL and CBM was searched from inception to 13 March 2022, for studies comparing the effect of GDFT with usual care on renal function in critically ill patients. GDFT was defined as a protocolized intervention based on hemodynamic and/or oxygen delivery parameters. A fixed or random effects model was applied to calculate the pooled odds ratio (OR) based on heterogeneity through the included studies. Results A total of 28 studies with 9,019 patients were included. The pooled data showed that compared with usual care, GDFT reduced the incidence of acute kidney injury (AKI) in critical illness (OR 0.62, 95% confidence interval (CI) 0.47 to 0.80, p< 0.001). Sensitivity analysis with only low risk of bias studies showed the same result. Subgroup analyses found that GDFT was associated with a lower AKI incidence in both postoperative and medical patients. The reduction was significant in GDFT aimed at dynamic indicators. However, no significant difference was found between groups in RRT support (OR 0.88, 95% CI 0.74 to 1.05, p= 0.17). GDFT tended to increase fluid administration within the first 6 h, decrease fluid administration after 24 h, and was associated with more vasopressor requirements. Conclusions This meta-analysis suggests that GDFT aimed at dynamic indicators may be an effective way to prevent AKI in critical illness. This may indicate a benefit from early adequate fluid resuscitation and the combined effect of vasopressors.