The aim of the study was to evaluate the activity of three cranberry (Vaccinium macrocarpon) ethanol solutions on Helicobacter pylori growth and urease activity. We included numerous clinical Helicobacter pylori isolates and three methods: agar well diffusion method (AWDM), disk diffusion method (DDM) and urease inhibition test (UIT). The results were expressed as differences in inhibitory zone diameters (AWDM and DDM) or urease inhibition duration (UIT) by cranberry solutions compared to the ethanol control. AWDM showed that 400, 40 and 4 mg/l cranberry extracts inhibited the growth of 82.1, 57.1 and 42.8% of the isolates, respectively, while DDM at the highest cranberry concentration suppressed only 39.3% of the isolates. At 400, 40 and 4 mg/l, cranberry extracts also inhibited urease activity of 63.6, 54.5 and 40.9% isolates within 10 min, but of fewer isolates (18.2, 13.6 and 9.1%, respectively) at the 45th min. Although cranberry activity was dose- and strain-dependent, it affected more than half of the isolates at the two highest concentrations. DDM was less effective in detecting this activity. The cranberry extracts also inhibited the urease activity of H. pylori; however, in most cases, the inhibition was only temporary. Briefly, the high cranberry activity against H. pylori, together with its anti-adhesive, antioxidant, anti-biofilm and anti-cancer properties, justifies its use for prophylaxis or adjunctive treatment of chronic H. pylori infection. Importantly, UIT results suggest the benefit of regular cranberry intake over random intake.