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Background: Kidney injury is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We hypothesized that measurement of molecular markers of tubular injury can diagnose COVID-19 associated kidney injury and predict a poor prognosis. Methods: This is a prospective cohort study of 444 consecutive COVID-19 patients in a New York City Emergency Department recruited in March and April, 2020. Urine and blood were collected simultaneously at hospital admission (median time of day 0, IQR 0-2 days) and within 1 day of a positive SARS-CoV-2 test in 70% of patients. Urine NGAL and KIM-1 assays were blinded to clinical data. Primary outcomes included the diagnosis of Acute Kidney Injury (AKI) as defined by AKIN criteria, as well as its duration and severity. Secondary outcomes included death, dialysis, shock, respiratory failure, and length of hospital stay. Kidney biopsies from COVID-19 patients were examined for biomarker gene expression. Results: Elevated urinary NGAL (uNGAL) levels were associated with SCr based AKI (267±301 vs. 96±139 ng/mL, P=1.6x10-10). uNGAL level >150 ng/mL had 80% specificity and 75% sensitivity to diagnose AKIN stage 2 AKI or higher. Higher uNGAL levels were associated with sustained AKI [aOR per SD of uNGAL (95%CI): 2.67 (1.81-4.06), P=1.8x10-6], need for dialysis (aOR: 3.67 (1.89-7.57), P=2.2x10-4), shock (aOR: 1.64 (1.26-2.15), P=2.9x10-4), prolonged length of stay (aHR: 1.22 (1.09-1.36), P=4.8x10-4), and death [aOR=1.62 (1.19-2.24), P=2.5x10-3], independent of baseline SCr and pre-existing co-morbidities. These associations were also preserved after adjusting for proteinuria measured in the same urine sample. NGAL is typically transcribed by distal nephron segments but in COVID-19 kidney biopsies with widespread histopathologic acute tubular injury (ATI), NGAL mRNA expression included proximal tubules. Conclusions: Elevated uNGAL in patients admitted with acute COVID-19 was associated with the development of AKI, increased severity and duration of AKI, the degree of histopathological acute tubular injury, shock, prolonged hospitalization, need for dialysis, and death.