© 2015 Wiley Periodicals, Inc. Objective: Using a large sample of colorectal cancer (CRC) survivors we 1) describe pain interference (PI) prevalence across the cancer continuum; 2) identify demographic and clinical factors associated with PI and changes in PI; and 3) examine PI's relationship with survivors' job changes. Methods: CRC participants of the Cancer Care Outcomes Research and Surveillance Consortium completed surveys during the initial phase of care (baseline,<1 year, n=2,961) and follow-up (about 1-year postdiagnosis, n=2,303). PI was measured using the SF-12 item. Multiple logistic regression was used to identify predictors of PI. Model 1 evaluated moderate/high PI at baseline, Model 2 evaluated new/continued/increasing PI postdiagnosis follow-up, and Model 3 restricted to participants with baseline PI (N=603) and evaluated predictors of equivalent/increasing PI. Multivariable logistic regression was also used to examine whether PI predicted job change. Results: At baseline and follow-up, 24.7% and 23.7% of participants reported moderate/high PI, respectively. Among those with baseline PI, 46% had equivalent/increasing PI at follow-up. Near diagnosis and at follow-up, female gender, comorbidities, depression, chemotherapy and radiation were associated with moderate/high PI while older age was protective of PI. Pulmonary disease and heart failure comorbidities were associated with equivalent/increasing PI. PI was significantly associated with no longer having a job at follow-up among employed survivors. Conclusion: Almost half of survivors with PI during the initial phase of care had continued PI into post-treatment. Comorbidities, especially cardiovascular and pulmonary conditions, contributed to continued PI. PI may be related to continuing normal activities, that is, work, after completed treatment.