Clinicians still wish to determine if H. pylori-infected patients have been cured after specific treatment. The present study aimed to evaluate the reliability of the H. pylori circulating antigen (HpCAg) test for noninvasive screening of H. pylori infection and assessment of cure after specific treatment. Sera of 134 symptomatic individuals (81 males & 53 females, aged 23-68 yr) were screened for HpCAg using ELISA. H. pylori infection was confirmed using a gold standard based on culture, rapid urease test, and histology testing. The detection rate of HpCAg was 69% among screened individuals. The gold standard confirmed H. pylori infection in 93% of individuals showing HpCAg in their sera. In addition, 31% of infected patients were excluded for their drug resistance. Eligible individuals received a standard triple therapy regimen including Lansoprazole, Clarithromycin, and Amoxicillin twice daily for 14 days. Six weeks later, the HpCAg testing was repeated to evaluate the treatment outcome. HpCAg was not detected in 78 % of treated individuals. Furthermore, the levels of HpCAg were significantly decreased (p < 0.001) in the sera of non-responders. In conclusion, the detection of HpCAg is a reliable non-invasive approach for screening and follow-up of H. pylori-infected individuals after treatment, especially in developing countries.