(1) There is evidence of the embryological, anatomical, histological, genetic and immunological differences between right colon cancer (RCC) and left colon cancer (LCC). This research has the general objective of studying the differences in outcome between RCC and LCC. (2) A longitudinal analytical study with prospective follow-up of the case-control type was conducted from 1 January 2010 to 31 December 2017 including 398 patients with 1:1 matching, depending on the location of the tumor. Inclusion criteria: programmed colectomies, 15 cm above the anal margin, adults and R0 surgery. (3) Precisely 6.8% of the exitus occurred in the first 6 months of the intervention. At 6 months, patients with LCC presented a mean survival of 7 months higher than RCC (p = 0.028). In the first stages, it can be observed that most of the exitus are for patients with RCC (stage I p = 0.021, stage II p = 0.014). In the last stages, the distribution of the deaths does not show differences between locations (stage III p = 0.683, stage IV p = 0.898). (4) The results show that RCC and LCC are significantly different in terms of evolution, progression, complications and survival. Patients with RCC have a worse prognosis, even in the early stages of the disease, due to more advanced N stages, larger tumor size, more frequently poorly differentiated tumors and a greater positivity of lymphovascular invasion than LCC
