Typhoid fever (TF) caused by Salmonella enterica subsp. enterica, serovar Typhi is a major public health concern in low-income countries. In Ethiopia, like any other sub-Saharan African country, the condition is worsened due to shortage of safe potable water and toilet access, low health education and overall high illiteracy level. The objective of this study was to estimate the prevalence of TF and its established risk factors in Masha town and its surroundings, northeast Ethiopia. In this health facility-based cross-sectional study design, all patients attending Masha Health Center (MHC) between October 2016 and February 2017 formed the source population and those clinically suspected of TF were successively recruited. A structured questionnaire was administered to capture socio-demographic, dietary and knowledge-related variables in association to the risk of TF. Blood samples collected, sera separated and tested by the slide-agglutination (Widal) method using commercially available S. typhi somatic (O) and flagella (H) antigens. Univariate and multivariate logistic regression models were used to test the association between socio-demographic variables and seropositivity for salmonella antigens used with p-value â‰¤0.05 considered statistically significant. Out of 490 patients diagnosed 346(70.6%) were TF seropositive the highest proportion (74.5%) of cases occurring among children 1-15 years followed by 16-45 years old adults (72.2%). Lower age (adjusted odds ratio (AOR) 2.259, 95% confidence interval (CI) 1.227-4.161, p=0.009), males 246(74.8%) TF positive with (AOR 2.064, 95% CI 1.301-3.275, p=0.002), lack of toilet 270(55.1%) from this 202(74.8%) TF positive with (AOR 1.713, 95% CI 1.331-2.906, p=0.037), and illiteracy 173(77.2%) TF positive with (AOR 3.940, 95% CI 1.926-8.063, p