BackgroundPuerto Rico, a US territory, faces numerous challenges adversely affecting public health, including poverty, a fragile healthcare system, inadequate infrastructure, a debt crisis, and vulnerability to climate change-related natural disasters. The impact of these factors on the Health-Related Quality of Life (HRQoL) measure has not been comprehensively evaluated. Only two studies have assessed HRQoL, with the latest conducted in 2011, prior to recent events that could affect public health. This study aimed to assess the HRQoL and associated sociodemographic and health risk factors among adults living in Puerto Rico in 2019.MethodsPrevalence and 95% confidence intervals were used to describe HRQoL and its associations with sociodemographic and health-related variables among adults living in Puerto Rico who answered the Behavioral Risk Factor Surveillance System (BRFSS) survey (n = 4,944) in 2019. Multivariable logistic regression models were developed to identify which of these variables were more likely to be associated with each of the four core HRQoL questions (HRQoL-4), expressed as prevalence odds ratios with 95% confidence intervals adjusted for potential confounders.ResultsThrough a comprehensive multivariable analysis, we uncovered significant risk factors – increasing number of chronic conditions, advanced age, and low income – associated with poor HRQoL among adults living in Puerto Rico. Specifically, our findings suggest that individuals with an increasing number of chronic conditions were more likely to report poor HRQoL across all 4 domains. As the number of reported chronic conditions increases by one, the odds of reporting having: fair/poor general health increased by a factor of 2.24 (POR: 2.24, 95% CI: 2.08–2.41), physical health impairment increased by a factor of 1.93 (POR: 1.93, 95% CI: 1.78–2.08), mental health impairment increased by a factor of 1.90 (POR: 1.90, 95% CI: 1.78–2.02) and activity limitation increased by a factor of 1.27 ( POR: 1.27, 95% CI: 1.13–1.42). Advancing age was associated with all domains of poor HRQoL, except for the mental health domain for which we observed higher rates of poor HRQoL among the younger population (POR: 4.76, 95% CI: 2.4–9.1).ConclusionThis paper shows that the prevalence of poor HRQoL has not improved compared to the only previous study of HRQoL of Puerto Rico in the last decade. We also found that poor HRQoL is associated with having multiple chronic conditions in adults living in Puerto Rico. This may be a consequence of a decline in health services after natural disasters and socioeconomic downturns on the island. The study emphasizes the need for targeted interventions and ongoing monitoring of the population’s HRQoL over time to reach vulnerable subgroups, especially those with chronic conditions, advanced age, and low income, in order to reduce health disparities in Puerto Rico.