PURPOSE: Adults with arthritis experience poor health-related quality of life (HRQOL), though research often focuses on single HRQOL outcomes or summary scores. We aimed to identify HRQOL profiles in adults with different arthritis types and determine risk and protective factors. METHODS: Data including PROMIS-29 Profile v2.1 and PROMIS Short Form v2.0 - Emotional Support 4a were collected through a national foundation's online survey of adults with arthritis in the U.S. We used latent profile analysis (LPA) to characterize the heterogeneity in arthritis patients by clustering them into HRQOL profiles, based on statistical model fit and clinical interpretability. We fit a multinomial logistic regression model with HRQOL profile assignment as the outcome to determine associations with protective and risk factors. RESULTS: We included 25,305 adults with arthritis. The LPA results favored a five-HRQOL profile solution (entropy = 0.83). While some profiles displayed better HRQOL in some domains, 93% of the sample displayed impacted pain and physical functioning. One profile (20%) displayed mean T-scores nearly 2 standard deviations below the population mean. Despite poor physical HRQOL outcomes, one profile (10%) displayed average mental health. All demographic and clinical factors contributed significantly to the model, including risk factors (arthritis types, work status) and protective factors (more emotional support, starting exercise). CONCLUSION: We identified profiles with consistently impacted HRQOL in arthritis, though one displayed average mental health functioning despite poor physical functioning. These results highlight the value of considering the patient's HRQOL experience alongside treatment options, and the potentially positive impact of non-pharmacological interventions.