Purpose: The purpose of this study was to identify latent classes of health-related quality of life trajectories in middle-aged women and investigate predictors for latent classes. Methods: This study utilized data from the 2nd, the 4th to the 7th Korean Longitudinal Survey of Women & Families. The subjects included 1,351 women aged 40~45 years. The data was analyzed using latent class growth analysis and logistic regression. Results: Two trajectories were identified for health-related quality of life in middle-aged women; ‘persistently good’ and ‘increasing’ groups. Predictors for the ‘increasing’ group were lower economic status, higher depression, and lower perceived health status. Conclusion: This study showed that characteristics of the individual, symptom status, and health perceptions were associated with health-related quality of life in middle-aged women. It is necessary to provide effective intervention for latent classes of health-related quality of life trajectories based on physical, mental, and social factors.