Hepatorenal syndrome (HRS) is characterized by functional renal failure in end-stage liver disease. Terlipressin is the drug of choice for treating type 1 HRS (HRS-1). It is expensive and often not readily available. We, in an open label, randomized, pilot trial, compared the efficacy of terlipressin and noradrenaline on the renal functions and clinical outcome of patients with HRS-1 and also sought predictors of response. PATIENTS AND Forty consecutive patients with HRS-1 were randomized to receive noradrenaline 0.5-3.0 mg/h and albumin (group A, N = 20) or terlipressin 0.5-2 mg, 6 hourly and albumin (group B, N = 20), until reversal of HRS (primary end point) or completion of 15 days of therapy (secondary end point). Systemic and renal parameters were monitored. Baseline parameters and delta creatinine at day 4 (DCD4) were used to predict response. The two groups were comparable at baseline. At similar time points, 10 (50%) patients in each group achieved primary end points. Patients in both groups had a significant (P < 0.05) decrease in serum creatinine from baseline (group A day 4 2.4 +/- 1.2 mg/dL, day 8 1.6 +/- 1.2 mg/dL, and day 15 1.0 +/- 0.4 mg/dL; group B day 4 2.5 +/- 1.5 mg/dL, day 8 1.8 +/- 0.9 mg/dL, and day 15 1.2 +/- 0.5 mg/dL) and progressive increase in creatinine clearance (group A day 4 26.5 +/- 12.8 mL/min and day 15 59.8 +/- 14.2 mL/min; group B day 4 31.4 +/- 21.4 mL/min and day 15 54.9 +/- 27.5 mL/min, P < 0.05). Median baseline plasma renin activity was reduced from 38.0 and 42.0 ng/mL/h to 3.0 and 8.0 ng/mL/h (P= 0.08) in groups A and B, respectively. Mean arterial BP and urine output significantly increased in both groups with therapy. Eleven (55%) patients in group A (10 responders) and an equal number in group B (8 responders) survived until day 15 (P= 0.798). Reversible cardiac ischemia was seen in one patient in each group. Noradrenaline therapy was significantly less expensive than terlipressin. On univariate analysis, the following baseline parameters predicted response to therapy: lower grade of encephalopathy, lower MELD score, higher creatinine clearance, higher mean arterial pressure (MAP), and lower plasma renin activity. However, on multivariate analysis only baseline creatinine clearance, MAP, and plasma renin activity were independent predictors of response. At day 4 of therapy, DCD4 was computed and a value of 0.15 mg/dL/day or more accurately predicted response. The sensitivity, specificity, positive predictive value, and negative predictive value for DCD4 0.15 mg/dL/day for predicting response to therapy were 90%, 75%, 78%, and 88%, respectively. Noradrenaline may be an effective and safe alternative to terlipressin in improving renal functions. Various baseline parameters and DCD4 can be used to predict response to therapy.