Background: To evaluate, in a context of innovative multidisciplinary clinical practice, the efficacy of oxaliplatin in adjuvant administration (chemotherapy, CT) in relation to the total administered dose, in terms of prognosis with other clinical and therapeutic factors, in the heterogeneous model of locally advanced rectal cancer (LARC), which is characterized by a risk pattern of dominant systemic progression. Methods: Observational-analytical, retrospective, unicentric, non-randomized study of two cohorts of patients receiving FOLFOX-4 induction CT in neoadjuvancy, radiochemotherapy and surgery, differing in that one cohort did not receive any adjuvant post-surgical treatment and the other one received adjuvant CT with FOLFOX-4 cycles. A total of 212 patients from the Radiotherapy Oncology Service at the University Hospital Gregorio Maranon were studied: the neoadjuvant CT treatment group with oxaliplatin consisted of 110 patients and adjuvant CT treatment group with oxaliplatin consisted of 102 patients. The median follow-up time for the whole study population was 72 months (6 years). Results: The sociodemographic, clinical and diagnostic characteristics were very similar in both cohorts of patients, but with a pattern of therapeutic selection towards elements of adversity in pathological post-neoadjuvant staging. The dose of oxaliplatin in adjuvance (postoperative) superior to 6 cycles was positively associated with the locoregional control (LRC) at 5 years (P=0.012) and with the overall survival (OS) (P=0.048) at 5 years. In the responders to neoadjuvance with oxaliplatin [patients with tumor regression grade (TRG 3-4)], the dose of oxaliplatin greater than 5 cycles in adjuvance (postoperative) was positively associated with OS (P=0.06). And the dose of oxaliplatin in the range of 4-5 cycles in adjuvance (postoperative) was positively associated with distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the cohort of responding patients (P=0.015 and 0.004, respectively). Conclusions: The contribution of adjuvant oxaliplatin in the oncological evolution shows a favorable effect of LRC, DMFS, DFS and OS in the subgroups of patients that exhibit elements of response to neoadjuvant oxaliplatin (categories TRG 3-4, and pN0, downstaging T, downstaging N). Therefore, this neoadjuvant response profile with oxaliplatin, measured with highly reliable methodology (validated microscopic pathological response scales), defines a population of oxaliplatin-sensitive patients who benefits significantly from the administration of adjuvant oxaliplatin in sufficient cumulative doses (more of 5 cycles).