Background <p>Helicobacter pylori is a globally prevalent chronic bacterial infection, disproportionately affecting low- and middle-income countries. Despite its significant gastrointestinal burden, epidemiological data from Afghanistan are limited. This study aimed to determine the prevalence, infection status, and associated factors of <i>H. Pylori</i> among adult dyspeptic patients in Jalalabad.</p> Methods <p>A cross-sectional study was conducted in Jalalabad, Afghanistan, from August 2023 to February 2024 among 363 adult dyspeptic patients. Cumulative <i>H. pylori</i> prevalence was defined by serum IgG and/or stool antigen positivity, active infection by stool antigen alone, and associated factors were identified using multivariable logistic regression (<i>p</i> &lt; 0.05) analysis.</p> Results <p>The cumulative prevalence of <i>Helicobacter pylori</i> infection was 79.1% (287/363), defined by combined serum IgG and/or stool antigen positivity. Infection status included chronic active infection (41.3%), acute infection (20.7%), prior exposure (17.1%), and non-infected status (20.9%). Independent factors associated with cumulative <i>H. pylori</i> infection were age ≥ 50 years (AOR = 6.50), married status (AOR = 3.90), low education (AOR = 2.20–5.80), multigenerational households (AOR = 7.30–7.50), crowded sleeping conditions (AOR = 2.30–4.50), family history of gastric disease (AOR = 8.90), low income (AOR = 4.80–9.20), and shared drinking glass use (AOR = 12.30). All associations were statistically significant (<i>p</i> ≤ 0.03).</p> Conclusion <p><i>H. pylori</i> affects 79.1% of dyspeptic adults in Jalalabad, with higher risk among older, married, low-education/income individuals, multigenerational households, crowded sleeping, shared drinking, or family history, highlighting the need for targeted interventions in this high-prevalence, resource-limited setting.</p> Clinical trial <p>Not applicable.</p>