A comparative cross-sectional study was conducted on 60 sewage workers and 30 matched unexposed referents from Mansoura city, Egypt, to estimate the prevalence and risk factors of Helicobacter pylori (H. pylori). Stool culture and detection of H. pylori antigen were done. In addition, the polymerase chain reaction (PCR) amplification of cytotoxin-associated gene A (cagA) gene in H. pylori in stool samples was carried out. The prevalence of H. pylori in sewage workers was 56.7% compared to 16.7% in the comparison group with a highly statistically significant difference between both groups. H. pylori cagA gene was present in 64.7% of H. pylori-infected sewage workers compared with 40% of controls. cagA gene was associated with more dyspeptic symptoms (77.3%) in infected workers compared to those of noninfected ones (33.3%) (P = .041). The risk of H. pylori was significantly higher among workers with poor compliance with personal protective equipment (PPE) (OR = 3.00), with duration of work > 20 years (OR = 4.71), older than 45 years (OR = 4.27), and of low education level (OR = 11.2). We concluded that H. pylori infection and heartburn with or without epigastric pain are significant health problems in the studied sewage workers. Low education and poor compliance with PPE were the only predictors of H. pylori infection in sewage workers.