Background: Approximately 21% of colon cancer patients have synchronous metastatic disease at presentation. Liver is by far the most common site of metastasis. For resectable and borderline resectable metastatic lesions after conversion to surgical resection, five-year survival ranges between 40-70%. Overall survival advantage of chemotherapy before and after metastasectomy of liver or lung lesion is not clear. We here compare the differential effect of neoadjuvant versus adjuvant chemotherapy on overall survival of patients who received resection of both primary and metastatic lesions in non-academic and academic settings from the National Cancer Database (NCDB). Methods: Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver or lung at diagnosis between 2010-2015 were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy within 1 year of diagnosis. Patients were categorized into 2 cohorts based on whether they received chemotherapy in the pre-operative/peri-operative setting (neoadjuvant chemotherapy –NAC) or post-operative setting (adjuvant chemotherapy AC). Descriptive analysis, Kaplan-Meier plots, Log-Rank tests, and Cox-regression models for multivariate survival analyses were performed. To assess uncertainty of estimates, a sensitivity analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3,038 colon cancer patients with liver or lung metastases were identified between 2010-2015. A larger majority of patients (n = 2387, 78.6%) received AC. The percentage of patients receiving NAC had steadily increased from 2010-2015 from 12.29% to 28.31%. The supermajority of metastases was in the liver. On multivariate analysis, patients who received NAC had an overall survival advantage (HR 0.661; 95% CI 0.534-0.879; P = 0.0001) in the non-academic setting whereas no advantage is seen in the patients treated in the academic settings (HR 0.994; 95% CI 0.831-1.189; P < 0.9484). The median overall survival for patients receiving NAC and AC was 47.24 months and 38.08 months respectively. Clinical factors associated with overall survival advantages in NAC patients treated in non-academic programs included age 20-49 years; low-income (< $38,000/year) status; CEA value of > 30; right sided colon primary; low T status and liver metastasis among others. The survival advantage of NAC over AC is associated with more clean resection margin and fewer regional lymph node involvement after surgery. Conclusions: Metastatic colon cancer with single organ liver or lung lesions benefits from neoadjuvant chemotherapy especially in non-academic settings based on our analysis of the NCDB database. The overall survival advantage in this setting has not been shown before.