Helicobacter pylori is the main cause of chronic gastritis, peptic ulcer, Mucosa Associated Lymphoid Tissue (MALT) lymphoma, and gastric cancer worldwide. Its prevalence is influenced by the socio-demographic characteristics, socio-economic status, hygiene, and lifestyle of the population. This study aimed to assess prevalence of Helicobacter pylori infections and its associated risk factors among adult dyspeptic patients visiting the outpatient department of Adet Primary Hospital, Yilmana Densa District, northwest Ethiopia. Hospital based cross-sectional study was conducted from February 10, 2022 to April 10, 2022. The study participants were selected using a systematic random sampling technique. Data were collected by pre-tested questionnaires. Blood and stool specimens were collected from each patient for antibody and H. pylori antigen tests, respectively. Data were analyzed using Statistical Package for Social Science (SPSS) version 26.0. Cohen‟s Kappa statistics was performed to assess the agreement of rapid serological test (anti- Helicobacter pylori IgG) with that of rapid stool antigen detection. A logistic regression model was used to assess the strength of association between Helicobacter pylori positivity and risk factors. The overall prevalence of Helicobacter pylori infection among adult dyspeptic patients in the study area was 64.8%. The sero- and feco prevalence of Helicobacter pylori infection was 62% and 51.1%, respectively with Kappa measure of substantial agreement 0.7. The sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of the serological test in reference to the stool antigen test was 94.7%, 72.1%, 78%, and 92.8%, respectively. Rural residence (AOR=5.55; 95% CI: 2.34-13.14; p<0.001), alcohol consumption (AOR=12.34; 95% CI: 2.29-66.51; p=0.003), having no awareness on H. pylori transmission (AOR=4.76; 95% CI: 1.86-12.15; P=0.001), using pond/river as source of drinking water (AOR=5.22; 95% CI: 1.91-14.27; p=0.001) and open field defecation (AOR=4.19; 95% CI:1.67-10.52; p=0.002) were the explanatory risk factors significantly associated with H. pylori infection. This study shows that the prevalence of H. pylori infection was very high. Therefore, education should be given to communities from where the current study participants were selected so as to increase their awareness on H. pylori infection, transmission, and associated major explanatory factors (consumption of alcohol, water source for drinking, and place of defecation) identified in the present study.