Purpose: The impact of lymphedema or related arm symptoms on health-related quality of life (HRQOL) in breast cancer (BrCa) survivors has not been examined using a large population-based cohort. Patients and Methods: The Iowa Women's Health Study (IWHS) collected self-report data for lymphedema, arm symptoms, and HRQOL (Medical Outcomes Study Short Form-36) in 2004 and data for cancer diagnosis, treatment, and behavioral and health characteristics between 1986 and 2003. We studied 1,287 women, age 55 to 69 years at baseline, who developed unilateral BrCa. We used cross-sectional analyses to describe the prevalence of lymphedema and arm symptoms and multivariate-adjusted generalized linear models to compare HRQOL (physical functioning, bodily pain, general health, physical and emotional role limitations, vitality, social functioning, and mental health) between the following three survivor groups: women with lymphedema (n = 104), women with arm symptoms without diagnosed lymphedema (n = 475), and women without lymphedema or arm symptoms (n = 708). Results: The mean (± SE) time between BrCa diagnosis and lymphedema survey was 8.1 ± 0.2 years. Of BrCa survivors, 8.1% self-reported diagnosed lymphedema, and 37.2% self-reported arm symptoms. Knowledge of lymphedema was low among survivors without diagnosed lymphedema (n = 1,183). After multivariate adjustment, women with diagnosed lymphedema or arm symptoms without diagnosed lymphedema had lower physical and mental HRQOL compared with women without lymphedema or arm symptoms. Effect sizes were mild to moderate. There was a dose-response relation between number of arm symptoms and lower HRQOL. Conclusion: In the IWHS, HRQOL was lower for BrCa survivors with diagnosed lymphedema and for those with arm symptoms without diagnosed lymphedema. Clinical trials are needed to determine what interventions can improve lymphedema and impact HRQOL for BrCa survivors.