Abstract Objective. Results from monitoring studies using biomarkers in blood samples aiming at early detection of recurrent colorectal cancer (CRC) are presently evaluated. However, some serological biomarker levels are influenced by the surgical trauma, which may complicate translation of the levels in relation to recurrence. The primary purpose of the present study was to evaluate the frequency of postoperative surgical interventions during a follow-up period of patients who have undergone surgery for primary CRC. Methods. In a prospective multicenter, clinical study, 634 patients resected for primary CRC were followed in the outpatient clinic every third month. Blood samples were drawn at each visit. A subgroup of 165 stage II and III patients, who had been followed for at least 3 years, was selected. Any recent surgical intervention associated with the primary disease and/or other diseases were recorded at each visit to the outpatient clinic. Results. Among the 165 patients, 49 developed recurrence (R+), 107 did not (R-) and 11 developed a new primary cancer, including 2 in the R+ group. Within the 3 years of observation, 78 (47.3%) of the 165 patients underwent 117 (range 1-5) postoperative surgical interventions. Seventy-five operations were related to CRC and 42 to benign diseases, while none were related to a new primary, malignant disease. Conclusion. Patients resected for CRC are frequently undergoing surgical procedures in the postoperative follow-up period. Therefore, postoperative monitoring using soluble biomarker levels, which may be influenced by the surgical trauma, must be adjusted in relation to postoperative surgical interventions.