Background: Multidrug-resistant tuberculosis (MDR-TB) is defined as resistance to at least isoniazid and rifampicin. In Cameroon, the prevalence is estimated at 150 cases/100,000 inhabitants or 6000 cases out of an estimated population of 3 million. Objective: The aim of the present study was to determine the risk factors associated with MDR-TB at Deido District Hospital located in the littoral region of Cameroon. Methods: This was a cross-sectional and analytical retrospective study. Our sample included all TB patients undergoing treatment at the Diagnostic and Treatment Center of the hospital from January 2019 to August 2020. Identified risk factors of MDR-TB were analyzed using the SPSS software version 20.0. Results: A total of 304 participants were enrolled with a predominance of 185 (60.8%) men. The average age was 35 years (29–43 years). About 122/304 (40%) of the patients suffered from MDR-TB. The significant factors associated with MDR-TB were occupation (adjusted odd ratio [aOR] = 61.46), monthly income (aOR = 0.11), history of TB (aOR = 5.3), alcohol consumption (aOR = 12.7); self-medication (aOR = 5.4) and consultation of traditional healers for any cure (aOR = 155.84). Conclusion: The emergence of MDR-TB associated with several risk factors in the study area is worrisome and can be prevented by improving the living conditions of patients and putting in place appropriate treatment strategies.