Background: Multi-drug resistant tuberculosis (MDR-TB) treatment failure is becoming a growing concern among health managers, clinicians, epidemiologists and health workers worldwide. Patients in this situation have a high probability of increasing drug resistance and extremely resistant forms of the disease, which put their health and their contacts’ at risk. Aim: To identify factors associated with multi-drug resistant tuberculosis (MDR-TB) treatment failure in a region of high prevalence in Peru. Methods: Analytical unpaired case-control study with a 1:2 ratio, including 90 cases and 199 controls. The evaluated factors were selected taking components of social determinants of health as references. The Odds Ratio (OR) was defined through bivariate and multivariate analysis. Results: Multivariate analysis showed four factors associated with treatment failure that corresponded to the human biological dimension: presence of cavities (AOR: 10.0, 95% CI: 1.3 -17.6); fibrous tracts in chest radiography (OR: 3.9, 95% CI: 1.1-10.9); pattern of resistance to five or more drugs in sensitivity test results (AOR: 4.1; 95% CI 2.9-5.7) and having received a second line treatment between seven and twelve months prior to the start of individualized treatment (AOR: 1.5; 95% CI 1.4 -1.6). Conclusions: These findings suggest, regarding MDR-TB case management, the need to direct efforts to promote early diagnosis and timely administration of highly effective treatment based on resistance patterns regarding MDR-TB case management.