To estimate the adherence of Western individuals to serum pepsinogen (PG) test and its accuracy in the detection of gastric cancer followed by upper gastrointestinal endoscopy. Individuals from the northern region of Portugal, aged between 40 and 79 years, were invited to participate in a blood collection for the determination of serum PG values by ELISA method (Biohit kits). Participants were classified into two groups: positive (PG I ≤70 ng/ml and PG I/ PGII ≤3) and negative (all others). All participants with a positive test and a consecutive random sample of participants with a negative test were subjected to endoscopy with biopsy. All the participants (positive or negative) subjected to endoscopy were followed up over 5 years. From a total of 13 118 participants, 5326 were men (41%) with a median age of 60 years, and 446 (3.4%) had a positive test. Of these, 274 (61%) were subjected to endoscopy. We observed six gastric cancers, five intestinal and one diffuse type, and three early gastric cancers, representing one cancer per approximately 2200 PG tests or one cancer per 74 positive tests. From these 240 participants with a negative test, three patients with gastric cancer were diagnosed during follow-up (an estimated negative predictive value of 99%). In this study, the PG test showed an estimated sensitivity, specificity, positive predictive value, and negative predictive value of 67, 47, 2, and 99%, respectively. Inhabitants of this high-risk region showed good adherence rate to a gastric cancer detection program based on a PG test followed by upper gastrointestinal endoscopy implemented for the first time. Accuracy estimates were similar to those in Japanese reports, indicating that this methodology could also be used effectively in Western countries with high rates of gastric cancer. Further formal cost-effective studies are however needed.