The ANSWER study reported that long-term albumin administration to patients with cirrhosis and uncomplicated ascites improves survival. Such treatment led serum albumin to increase within a month, remaining stable thereafter. This post-hoc analysis aimed at determining whether on-treatment serum albumin could guide therapy.Logistic regression was used to assess the association between baseline serum albumin and mortality and determine on-treatment factors associated with mortality and predicting the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and 2nd-order polynomial regression. Patients failing to normalise on-treatment serum albumin were compared with a subset of patients from the control arm matched by principal score.Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. 2nd-order polynomial regression revealed that survival improved in parallel with 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dL intervals) in the range 2.5-4.5 g/dL discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dL. Even those patients who failed to normalise serum albumin had a better survival than untreated patients.Baseline serum albumin per se should not guide the decision to start albumin therapy. Contrarywise, 1-month on-treatment serum albumin is strongly associated with outcomes and could be used as a guide in order to improve the use of albumin, 4.0 g/dL being the target threshold to be pursued. However, even patients failing to normalise serum albumin take advantage from long-term albumin administration.