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PURPOSE This study aimed to evaluate the association between acute kidney injury (AKI) and 6 months neurological outcome after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS Prospective multi-center observational cohort included adult OHCA patients treated with targeted temperature management (TTM) across 20 hospitals in the South Korea between October 2015 and October 2017. The diagnosis of AKI was made using the Kidney Disease: Improving Global Outcomes criteria. The outcome was neurological outcome at 6 months evaluated using the modified Rankin scale (MRS). RESULTS Among 5676 patients with OHCA, 583 patients were enrolled. AKI developed in 348 (60%) patients. Significantly more non-AKI patients had good neurological outcome at 6 months (MRS 0-3) than AKI patients (134/235 [57%] vs. 69/348 [20%], P < .001). AKI was associated with poor neurological outcome at six months in multivariate logistic regression analysis (adjusted odds ratio: 0.206 [95% confidence interval: 0.099-0.426], P < .001]). Cox regression analysis with time-varying covariate of AKI showed that patients with AKI had a higher risk of death than those without AKI (hazard ratio: 2.223; 95% confidence interval: 1.630-3.030, P < .001). CONCLUSIONS AKI is associated with poor neurological outcome (MRS 4-6) at 6 months in OHCA patients treated with TTM. TRIAL REGISTRATION NCT02827422.