Background: The expansion of the cancer survivor population in the U.S. mandates better understanding of survivors’ symptoms. Methods: A sample of 3106 ambulatory patients diagnosed with invasive cancer of the breast, prostate, colon/rectum or lung were recruited from six academic medical centers and 32 community sites at any point in their disease trajectory. A subgroup of cancer survivors (n = 248, 8%) defined as having non-advanced cancer, not currently receiving treatment, and diagnosed at least 3 years prior to study registration were identified. Participants rated symptom severity on a 0-10 scale for 25 common cancer-related symptoms at study enrollment and 4-5 weeks later. Symptom burden was compared to remaining patients in the sample (n = 2,858). Results: Survivors (n=248) had a median age of 64 years and were predominantly White (76%) and female (75%). Primary cancer site included breast (63%), colorectal (19%), prostate (9%) and lung (8%). Most of the sample had a performance status of 0 (76%). Most survivors were greater than 5 years from diagnosis (63%) and 38% were 3-5 years from diagnosis. Survivors reported a mean of 1.5 moderate to severe symptoms at enrollment and follow-up and the most common moderate to severe symptoms were fatigue (16%, 19%), disturbed sleep (15%, 20%), cognitive difficulties (13%, 14%), pain (13%, 13%), and drowsiness (9%, 15%). There were no significant predictors for fatigue or cognitive difficulties. Performance status predicted sleep disturbance (OR 0.28, p=0.0047). The odds that a patient 64 or younger reported moderate to severe drowsiness was 9.9 times that of an older patient (p=0.002). Conclusions: Prospective assessment of a national cohort of cancer survivors predominantly treated in community settings indicate that many survivors experience ongoing symptom burden despite significant time (> 3 years) since diagnosis and absence of ongoing need for cancer treatment. The most common moderate to severe symptoms included fatigue, disturbed sleep, cognitive difficulties, pain and drowsiness. These findings, particularly predictors of long-term symptom burden, can inform ongoing efforts to improve survivorship care and research.