Aim To assess the changes in health-related quality of life in patients discharged from the intensive care unit (ICU). Methods At the General University ICU, Trauma Hospital in Athens, 242 patients were enrolled prospectively over a study period of 18 months. Out of these, 116 participants (47.9%) completed all survey components at 6, 12, and 18 months. We used Quality of Life-Spanish (QOL-SP) to assess the health-related quality of life. Patients or their relatives were interviewed on ICU admission and at 6, 12, and 18 months after discharge from the ICU. Results Mean quality of life score of the patients increased from 2.9 +/- 4.8 ( out of maximum 25 points) on ICU admission to 7.0 +/- 7.2 points at 6 months after discharge, and then decreased to 5.6 +/- 6.9 points at 18 months (P < 0.001 ;Friedman Test). Multilinear regression analysis showed that the variables which had the strongest association with the quality of life on admission were age ( P = 0.002) and male sex ( P = 0.001), whereas age ( P < 0.001), length of ICU stay ( P < 0.001), and male sex ( P = 0.002) had the strongest association 18 months after discharge from the ICU. Survival rate was 66.9% at discharge from ICU and 61.6% at hospital discharge. There were 33% deaths in the ICU, 5.3% in the hospital, and 6.2% after ICU discharge. There were 7.4% patients lost to follow-up. Conclusions After discharge from the ICU, patients' quality of life was poor and showed an improvement at 18 months after discharge, but was still worse than on admission. Age, ICU length of stay, and male sex were the factors that had the strongest impact on the quality of life on admission and at 18 months after discharge from the ICU.