Background: The initial management of dyspepsia is shifting away from the invasive endoscopic biopsy procedure to identify H. pylori before eradication treatment. A test-and-treat strategy is firmly in place, but choices can be limited in resource constrained environments. Objective: To investigate the short term effect of blind eradication therapy in management of dyspeptic patients prior to knowledge of H. pylori infection status by serology and histology. Patients: A cross sectional study of 125 consecutive patients presenting at a tertiary facility with dyspepsia were screened for other diseases and then offered blind triple H. pylori eradication therapy. Methods: Participants underwent clinical evaluation and completion of a structured questionnaire eliciting sociodemographic, smoking and drinking habits and drug history. Stored sera were tested for liver transaminases, total protein, albumin, creatinine, urea, Hepatitis B surface antigen, Hepatitis C virus antibody and H. pylori IgG antibody by ELISA at the end of recruitment, while stool microscopy, occult blood test and abdominal ultrasound scan were done before upper gastrointestinal endoscopy, where antral biopsy specimens obtained were processed for H. pylori identification and histological assessment. Patients received oral amoxicillin 1g and clarithromycin 500mg twice daily or metronidazole 400mg three times daily (in place of clarithromycin) and omeprazole 20mg twice daily for fourteen days andcame for follow-up at two and four weeks for assessment of treatment response. Data were entered into a computer and analysed using SPSS Version 16. Descriptive statistics, Chi- square test with Yates correction, t-test, ANOVA and the Cochran-Mantel Haenszel test to compare proportions of treatment success were used. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined. P values __ampersandsignlt; 0.05 were considered significant. Results: All patients (125) completed the study, 76 (60.8%) were females and the mean age of subjects was 35.3 __ampersandsignplusmn; 12.70 years (range 18 __ampersandsignndash; 84); 74.4% of respondents were __ampersandsignlt; 42years of age and 90% __ampersandsignlt; 55 years. H. pylori were detected by histology in 100 (80.0%) patients, 99 of whom were among the 117 (93.6%) positive by serology (Sensitivity 99%, PPV 84.6%, efficiency 84.9%). Endoscopy was normal in 5% of patients and gastritis 39.5%, oesophagitis 27.7%, and duodenitis 22.7%. The relationship between chronic gastritis inflammatory activity and H. pylori infection status was highly significant. Chi square X2 = 24.33 p= 0.000001; Yates correction X2 = 20.04 p=0.000008. Symptom improvement was highly significant at both 2 and 4 weeks from baseline and between the two visits. (p=.000). Cochran-Mantel Haenszel test to compare proportions of treatment success by H. pylori status was highly significant (Q=112.067 p=.000) Conclusion: On a short term basis, blind empirical H. pylori eradication therapy is effective in the management of dyspeptic patients in a high prevalence area and can obviate the need for testing before treatment. Serology concurred very well with histology as a method of infection identification.