Background: Adjuvant chemotherapeutic treatment of UICC-stage III/IV colon cancer with fluorouracil, leucovorin and oxaliplatin (FOLFOX) is widely accepted as the current standard after R0-resection. However, with continuous improvement of patients´ survival and life expectancy, long-term side effects of chemotherapy such as second cancer development are becoming increasingly important. Methods: We performed a retrospective analysis of clinical data derived from the population-based cancer registry at the Regensburg Tumor Center, Germany. Patients who were diagnosed with colon cancer UICC stage III and IV between 2002 and 2018 and underwent R0 surgical resection of primary tumor were included for the study. Second cancer was as defined new tumor occurrence at least 6 months after beginning of chemotherapy and in another localization compared to primary tumor. Second cancer rate was compared between patients with and patients without adjuvant chemotherapy. Results: Data of totally 2,856 Patients with UICC-stage III/IV colon cancer were analyzed, 1,520 (53.2%) of whom received adjuvant chemotherapy. Overall, 223 (7.8%) patients developed a subsequent second cancer. Most frequent second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancers (8.1%), lung cancer (8.1%), rectal cancer (4.9%) and uterine cancer (4.9%). However, patients treated with adjuvant chemotherapy did not have a significantly increased risk for second cancer development compared to patients without adjuvant chemotherapy (Table). Interestingly, our data suggest a significantly decreased second cancer rate in patients treated with FOLFOX compared to FUFOL for adjuvant treatment. Conclusions: Second cancer development was not increased after adjuvant chemotherapy for UICC-stage III/IV colon cancer, which is a novel aspect in the ongoing discussions on reduction of adjuvant treatment to 3 months or treatment of lymph node negative patients. Primary tumor (N) Second tumor (N) Second tumor (%) Cumulative rate 60 months (%) Log-Rank p Chemotherapy Yes 1520 145 9.5% 8.8% No 1336 78 5.8% 9.0% 0.685 Total 2856 223 7.8% 8.9%