Helicobacter pylori is causally associated with gastritis and peptic ulcer diseases. Recent data (meta-analysis) have demonstrated that triple therapy with amoxicillin, clarithromycin, and a proton pump inhibitor has an eradication rate of only 74-76% and new therapeutic protocols may be necessary. The aim of this study was to examine whether adding bovine lactoferrin (bLf) and probiotics (Pbs) to the standard triple therapy for H. pylori infection could improve the eradication rate and reduce side effects. H. pylori infection was diagnosed in 206 patients: in 107 based on an upper endoscopy exam and a rapid urease test, and in 99 by means of the H. pylori stool antigen-test and the C(13) urea breath test (C(13) UBT). The patients were randomized into two groups: 101 patients (group A) underwent standard triple eradication therapy (esomeprazole, clarithromycin, amoxicillin), while 105 patients (group B) underwent a modified eradication therapy (standard triple eradication therapy plus bLf and Pb). Successful eradication therapy was defined as a negative C(13) UBT 8 wk after completion of the treatment. Results were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis. Data were evaluated and considered positive when P<0.05. At the end of the study 175/206 patients showed negative C(13) UBT results. According to intention-to-treat analysis, the infection was eradicated in 73/101 patients from Group A and in 93/105 from Group B. PP analysis showed 73/96 patients from Group A and 93/101 from Group B to have been successfully treated. More patients from group A than from group B reported side effects from their treatment (P<0.05). The results of our study suggest that the addition of bLf and Pbs could improve the standard eradication therapy for H. pylori infection--bLf serving to increase the eradication rate and Pbs to reduce the side effects of antibiotic therapy.