In patients with acute kidney injury (AKI), serum creatinine level does not increase until moderate to severe reduction in glomerular filtration rate (GFR) occurs. Thus its use for estimating GFR in early AKI delays detection of kidney damage and making important therapeutic decisions. Moreover, serum cystatin C is not affected by gender, age, race, and muscle mass and also does not suffer from lag period for its rise in early AKI. We studied 200 healthy subjects and 130 AKI patients over a period of 2 years at a tertiary care hospital. Serum creatinine and serum cystatin C were studied and analyzed in relevance to early AKI. We found that 56.2% of patients of AKI group had normal levels of serum creatinine in early phase, while all patients had elevated serum cystatin C at same time. Multiple logistic regression analysis revealed cystatin C-based GFR reflecting decline in GFR with worsening AKI in better than creatinine-based GFR. Serum cystatin C is a better marker of renal function in early stages of AKI and is less affected by age, gender, muscle mass, and ethnicity. Its use helps in early therapeutic intervention and possibly favorable outcome.