We examined the value of NGAL for predicting clinically relevant WRF and outcomes in 1447 patients admitted with AHF (to our knowledge, the largest cohort of AHF patients with available serial plasma NGAL measurements). WRF was common, occurring in 22% of patients during the first four days of admission. Patients who developed WRF were more likely to have poor renal function at baseline, although only NGAL levels—but not creatinine—were independently associated with the development of WRF. We found no indication that plasma NGAL rises earlier than creatinine in AHF patients who develop WRF; both markers rose in tandem over the first two days of admission. Although NGAL showed statistically significant incremental value for predicting WRF, no combination of markers performed particularly well, with AUCs below 0.60. While high levels of both NGAL and creatinine at baseline were associated with mortality and rehospitalization, neither was independently predictive after adjustment for clinical covariates.