Objective: To identify health-related quality of life (HRQOL) trajectories during 18 months of predialysis care and associated patient characteristics and illness perceptions. Method: 396 incident predialysis patients participating in the prospective PREdialysis PAtient REcord-2 study completed every 6 months the 36-item Short Form Health Survey (i.e., mental and physical HRQOL) and Revised Illness Perception Questionnaire. HRQOL trajectories were examined using latent class growth models, and associated baseline factors were identified using logistic regression. Analyses for illness perceptions were adjusted for demographic and clinical characteristics. Results: Three physical HRQOL trajectories (low-stable [34.1% of the sample], medium-declining [32.5%], and high-increasing [33.4%]) and two mental HRQOL trajectories (low-stable [38.7%] and high-stable [61.3%]) were identified. Increased odds for a low-stable physical HRQOL trajectory were detected in older patients (Odds ratio [OR] = 1.04), patients with cardiovascular disease (OR = 2.1) and patients who believed to a lesser extent they can personally control their disease (ORadj = 0.88). Increased odds for both a low-stable physical and mental HRQOL trajectory were detected in patients who believed to a higher extent that their disease is cyclical, has negative consequences, causes negative feelings, and in patients who believed to a lesser extent they understand their disease (ORadj ranged between 0.84 and 1.36). Additionally, patients who attributed more symptoms to their disease had increased odds for a medium-declining (ORadj = 1.21) and low-stable physical HRQOL trajectory (ORadj = 1.50). Conclusions: Older age and cardiovascular disease are markers for unfavorable physical HRQOL trajectories, and stronger negative illness perceptions are markers for unfavorable physical and mental HRQOL trajectories. Targeting negative illness perceptions could possibly optimize HRQOL during predialysis care.