Introduction: Failure to treat microscopy-positive pulmonary tuberculosis (MPT+) poses a risk to public health through the spread of infection and could be a gateway to anti-tuberculosis drug resistance. The aim of this study was to describe the epidemiological characteristics of PMT+ TB patients with treatment failure, to measure the degree of association between the various factors and TB treatment failure, and to formulate recommendations for improving NTP activities. Methods: This is a retrospective case-control study conducted from 1 January 2010 to 31 December 2020 at the CDTMR of the General Referral Hospital of Beni. The cases are patients treated for PMT+ and who had a therapeutic failure. Three controls for each case were selected among patients with PMT+ who were declared cured. Data analysis was performed using Epi-Info version 3.5.3 for Windows. Results: 128 patients were included in the study. 32 patients were treatment failures. The mean age of cases and controls was 42 years (+/- 14), the M/F sex ratio was 31 and 2.4 in cases and controls respectively, urban residents accounted for 90.3% and 83.2% in cases and controls respectively. Bivariate analysis showed a significant association between treatment failure and weight loss at first control (OR=1.55), non-decrease in bacillary density at first control (OR=25.5) and treatment discontinuation (OR=20.5). After adjustment, weight loss of 1 kg (adjusted OR=1.92), no decrease in BAAR density (adjusted OR=8.30) and treatment discontinuation (adjusted OR=12.2) remained significantly associated with treatment failure. Conclusion: Active surveillance should be instituted in TB patients with PMT+ who present at first check-up with weight loss, non-decrease in bacillary density on direct examination and/or a notion of treatment discontinuation.