OBJECTIVES There have been a number of new drugs and biologicals approved by the FDA in the last five-years for the treatment of colorectal cancer (CRC). Objective of this study was to compare the initial treatments and overall medical costs for working-age persons with CRC before and after the introduction of these treatments. METHODS This retrospective cohort study was based on a large administrative database and included patients with an ICD-9 diagnosis of CRC. We looked at individuals treated for CRC in the period prior to introduction of new chemotherapy and biological agents (January 2002-December 2002) and the period after the introduction of two biologicals (bevacizumab and cetuximab) and one chemotherapy agent (oxaliplatin), (June 2004-May 2005). We assigned patients to stage of diagnosis based on treatment regimens. We identified 2545 patients (61% Stage III) with CRC in the pre-period and 4413 patients (59% Stage III) with CRC in the post-period. We estimated mean total medical costs in the pre- and post- periods using the Kaplan-Meier sample average estimator. RESULTS The predominant treatment regimen in the pre-period for stage III CRC was 5-FU/Leucovorin (77%), while the pre-dominant regimens the post-period were 5-FU/Leucovorin (36%) and FOLFOX (35%). The pre-dominant treatment regimen for stage IV CRC was IFL/FOLFIRI (50%), while the most common regiments in the post-period were IFL/FOLFIRI (22%) and FOLFOX (23%). Additionally, over 14% of the patients received a biological agent in the post-period. There was also a significant increase in total medical costs over this time period. The mean costs for Stage III and Stage IV CRC patients increased from $56,187 in the pre-period to $101,049 in the post-period (p<0.001). CONCLUSIONS The introduction of new treatments for CRC significantly changed the treatment patterns for both Stage III and Stage IV CRC. These changes in treatment were accompanied by a significant increase total medical costs.