Background: Co-infection of Objective: To explore the prevalence and associated variables of MTB/HIV co-infection among PTB presumptive patients in Northwest Ethiopia. Methods: From February to August 2021, a cross-sectional institutional investigation was conducted at the Metema and Abrehajira hospitals. Semi-structured questionnaires were used to collect socio-demographic and clinical data. The MTB/RIF Xpert assay was used to process sputum, and 3 ml of veins blood was collected for HIV rapid test (STAT-PAK, ABON, and SD BIOLINE HIV test algorithm) following the Ethiopian National HIV test algorithm. The Gene Xpert assay's sample processing control was checked to ensure data quality. Data entered into Epi-Data were exported to SPSS version 20 for analysis. Statistically significant variables (p-value ≤0.2) from bivariable analysis were included in multivariable analysis. A Results: This study included 314 PTB presumptive patients with a median age of 35.0 years, of which 178 (56.69 %) were males. Among all patients, 40(12.7 %) and 51(16.2 %) were PTB, and HIV seropositivity, respectively. Of the PTB patients, 14/40 (35 %) (95 % CI: 24.4-45.6) were co-infected with HIV/AIDS. Married patients were 70 % less likely than unmarried individuals (AOR = 0.3 CI; 0.07-0.98) to have MTB/HIV co-infection. Patients who had contact history with MDR-TB patients (AOR = 5 CI; 1.37-18.00), and those who had a history of alcohol use (AOR = 12.2 CI; 2.56-57.8) were more likely to have MTB-HIV co-infection than their peers. Conclusion: Our findings showed that MTB-HIV co-infection is one of the most important community health concerns in the study area. Therefore, MTB/HIV cooperation activities should be fully in place to prevent co-infection and its impact on the population.