Currently, there is a lack of data related to differences in symptoms and infection across different types and anatomical sites of lymphedema. The objective of this study was to examine differences in symptoms and infection status among individuals with lymphedema of the upper or lower extremities. The National Lymphedema Network initiated an online survey of self-report lymphedema data from March 2006 through January 2010. Descriptive statistics, Mann-Whitney tests, and Chi-square tests were used to analyze data. 723 individuals with upper extremity lymphedema and 1114 individuals with lower extremity lymphedema completed the survey. Individuals with extremity lymphedema experienced high symptom burden and infectious complications. Compared with individuals with upper extremity lymphedema, individuals with lower extremity lymphedema experienced more frequent and more severe symptoms (p<.001), infection episodes (p<.001), and infection-related hospitalizations (p<.001). No statistically significant differences of symptom burden and infection status were identified between individuals with lower extremity primary and secondary lymphedema. Individuals with extremity lymphedema experience substantial symptom burden and infectious complications; however, those with lower extremity lymphedema have more severe symptoms and more infections than those with upper extremity lymphedema.