Purpose Illness cognitions regarding helplessness and acceptance are known to play a role in health-related quality of life (HRQoL). Our study examined the evolution of these illness cognitions and the physical (PQoL) and mental QoL (MQoL) in liver transplantation (LT) patients over time in relation to pre-and postoperative clinical factors. Methods We performed an analytical cross-sectional study using self-report questionnaires at 4 timeframes: preLT, postLT 0-3 m , postLT 1y , and postLT 2y . T-test was used to identify the influence of different clinical factors related to the LT on postLT 2y QoL and illness cognition. Linear mixed models were used to determine evolution. Results PostLT patients showed significant less helplessness and more acceptance cognitions. PQoL and MQoL decreased postLT 0-3 m, then started to increase and are highest at postLT 1y. Patients with preLT ascites showed significantly less helplessness postLT 2y , while patients with a low preLT MELD score < 20 showed a significant better MQoL postLT 2y . Biliary complications and re-transplantation were associated with more helplessness and a worse PQoL postLT 1y-2y . Length of stay in ICU and hospital was negatively correlated with illness cognitions and PQoL and MQoL postLT 1y. Conclusions Our findings confirm that liver transplant patients have improvement of illness cognitions and mental and physical HRQoL at 1 and 2 years after liver transplantation. A postoperative period without complications and with short stay in ICU and in hospital, is important to achieve PQoL and feeling less helpless, while the MQoL is influenced by acceptance and preLT PQoL. Multidisciplinary approach preLT and postLT should be standard care. Keywords Liver transplantation • Health-related quality of life • Illness cognitions • Acceptance • Length of stay Abbreviations AIH Auto-immune hepatitis. ALD Alcoholic liver disease. ALF Acute liver failure. CMV Cytomegalovirus.