Background This study assessed the effectiveness of computerized measurement and feedback of health-related quality of life (HRQoL) in daily clinical practice in patients with chronic liver disease. Methods One hundred and sixty-two patients (61% men; mean age 47.5 years) regularly completed computerized HRQoL questionnaires before each consultation for the duration of 1 year. Six physicians were randomly assigned to the experimental group and received an instant online graphical output of data. Five other physicians were randomly assigned to the control group and conducted their consultations as usual. Differences between groups on generic- and disease-specific HRQoL, patient management, and patient satisfaction with the consultation were assessed, as were physicians’ experiences with HRQoL data and effects on their consultations. Results No direct effect of the experimental condition on patients’ HRQoL was found. However, an interaction effect of the experimental condition and age was found: older patients in the experimental group had significantly better disease-specific HRQoL (F = 4.16; P = 0.04) and generic mental HRQoL (F = 4.62; P = 0.03) than patients in the control group. Also, male patients in the experimental group had better generic mental HRQoL than patients in the control group (F = 6.10; P = 0.02). Physicians in the experimental group altered their treatment policy significantly more often than did physicians in the control group (z = −3.73, P = 0.00), and their experiences with the availability of HRQoL information were generally positive. The scores on patient satisfaction with the consultation did not differ significantly between the experimental and control groups (z = −1.20, P = 0.23). Conclusions Computerized measurement and feedback of HRQoL in a daily clinical practice of an outpatient department of hepatology did not improve HRQoL for the entire group of chronic liver patients but, rather, improved disease-specific HRQoL of older patients with chronic liver disease and mental HRQoL of older patients and male patients with chronic liver disease. It also had an effect on patient management.