Objective: To determine if patients’ insurance status or the income level of their zip code of residence affect their quality of life or overall survival after enrollment in clinical trials for cancer treatment. Methods: Data were collected from cancer treatment trials conducted through the North Central Cancer Treatment Group and the Alliance for Clinical Trials in Oncology. 700 subjects with baseline quality of life scores were analyzed to explore potential differences in quality of life indicators by insurance group. 624 patients with valid US zip codes were also analyzed based on the median household income of their zip code to determine any associations with quality of life. Overall survival was also analyzed by insurance group and by income quartile. Results: 700 subjects (mean age 59 years, 53% male) were included. 49% had private insurance only, 30% had public insurance only, 8.9% had both private and public insurance, 1.4% had no insurance, and 10% had other insurance. 13% of patients came from zip codes in the bottom quartile by median income, 20% came from the second quartile, 25% from the third quartile and 42% from the top quartile. No significant differences were found in baseline quality of life scores between insurance groups or income quartiles. Patients with both private and public insurance had higher baseline fatigue scores compared to only private, only public, or other insurance. No significant difference was found in baseline fatigue scores by income quartile. No significant differences were found in overall survival by insurance group or income quartile. Conclusions: Patients with both private and public insurance may need more extensive interventions than patients with other insurance statuses due to their higher baseline fatigue scores. Future studies are needed to further investigate the effects of neighborhood advantage level on quality of life indicators.