BackgroundFor early detection of cancer, we have previously developed the AminoIndex Cancer Screening (AICS) system, which quantifies 6 plasma-free amino acids (PFAAs) in blood samples. Herein, we examined the usefulness of the AICS in patients with colorectal cancer (CRC) by comparing the preoperative and postoperative PFAA profiles.MethodsOur study cohort consisted of 62 patients who had undergone curative resection for CRC at our cancer center, with no recurrence at the time of the study. Blood samples were collected from fasted patients within 1 week before the resection and at 0.5–6.5 years post-resection. Following plasmapheresis, the PFAA levels were measured via liquid chromatography/mass spectrometry, and the AICS values were computed (the higher the value, the greater the probability of cancer). Risk was calculated from the AICS value and ranked as A, B, or C, with rank C representing the highest risk. All patients in our study were rank B + C.ResultsThe postoperative AICS value was lower than the preoperative value in 57 of the 62 patients; the rank was also lower postoperatively (49 patients, p < 0.001). The decline in both was stage-independent, even occurring in patients with right-sided tumors or poorly differentiated adenocarcinomas. For comparative purposes, the levels of 2 tumor markers (carbohydrate antigen 19–9 and carcinoembryonic antigen) were also examined; these were within the reference ranges in 70–80% of patients preoperatively and in 80–90% postoperatively.ConclusionWe suggest that tumor-bearing conditions alter the PFAA profiles, which may be used to predict prognosis and monitor for recurrence in CRC patients after tumor resection.Trial registrationThis trial has been retrospectively registered at UMIN-CTR R000028005, Oct 06, 2016.Electronic supplementary materialThe online version of this article (10.1186/s12893-018-0344-0) contains supplementary material, which is available to authorized users.