OBJECTIVES: To compare incremental costs of laparoscopic and open surgery for rectal cancer within a large randomized trial (COLOR II) with long-term follow-up. METHODS: Data of clinical resource use from the randomized controlled trial COlorectal cancer Laparoscopic or Open Resection (COLOR) II was used to perform a prospective cost-minimization analysis. Some data were retrospectively collected for COLOR II-patients operated at the largest participating Swedish hospital (n=105). Sick leave data was provided by the Swedish social insurance agency. Unit costs were collected from Swedish sources. The primary outcome was the difference in mean cost between laparoscopic and open surgery. One-way sensitivity analysis was used to check robustness of the results. RESULTS: The COLOR II trial enrolled 1044 rectal cancer patients between 2004-2010 randomized between laparoscopic and open surgery 2:1. At the three-year follow-up data for the clinical variables used in the analysis were available for 74-89 % of patients. Laparoscopic surgery was more costly to the health care sector than the open technique, both at 28 days ($1910, 95% CI: 677 to 3143) and three years ($3854, 95%CI: 1527 to 6182) after surgery. There were, however, no differences in long-term costs to society between laparoscopic and open surgery ($684, 95% CI: -5799 to 7166). Results were sensitive to length of hospital stay, sick leave and the cost for stoma materials as demonstrated in one-way sensitivity analysis. CONCLUSIONS: The study found short and long-term cost differences for the health care sector. There was no significant difference in regards to long-term societal perspective. Future research is suggested to investigate the effects of sick leave costs using material from a greater number of patients.