OBJECTIVES: To evaluate the health-related quality of life (HRQOL) and to compare direct medical, non-medical and indirect cost of stage III colorectal cancer(CRC) patients receiving either capecitabine-based or 5-FU/LV-based adjuvant treatments from societal perspective. METHODS: An observational follow-up study to collect HRQOL and cost data from stage III CRC patients were conducted in 12 hospitals from 2008 to 2010. A total of 535 patients were invited to complete questionnaires during the study period: at study baseline (Q0), at 3 months after the initial adjuvant treatment (Q3), and at 1 month after treatment had finished (Q7) using the EORTC QLQ-C30 and QLQCR-38 questionnaires. Cost data were obtained from National Health Insurance Research Database (NHIRD), patient questionnaire (Q3) and productivities loss from Manpower Utilization Survey.  66% of patients completed the questionnaire as per protocol and their data were the basis for further analysis. Propensity score matching (PSM) method was used to reduce selection bias and to avoid endogenous problems by matching variables, i.e. age, gender, location of tumor, marital status, education, work and the number of comorbidities between two groups. After PSM, a total of 239 patients were analyzed. RESULTS: In capecitabine-based treatment, Physical, Role, Emotional, Social, Global Health status, Body Image, Future perspective Functioning, Fatigue, Pain, Diarrhea, Stoma-related problem, and Weight loss Symptoms were all improved from Q0 to Q3 and Q0 to Q7. In 5-FU/LV-based treatment, Physical, Role, Social, Global health status Functioning, GI tract and Weight loss Symptoms also improved. Total direct medical, direct non-medical, and indirect cost of capecitabine-based and 5-FU/LV-based treatment were NT$29,452 (USD $982) and NT$55,200 (USD $1,840), respectively. CONCLUSIONS: This real-life study shows that adjuvant chemotherapy has no negative impact on HRQOL during study period. Capecitabine-based treatment performs better in most functioning aspects of HRQOL and is cost-saving in direct and indirect resources utilization from societal perspective.