Helicobacter pylori (Hp) management has undoubtedly resulted in a notable economic burden on healthcare systems globally, including Greece. Its cost has never been estimated so far, especially during the recent 10-year unprecedented financial crisis. Direct medical and procedural costs for one attempt “outpatient” Hp eradication treatment were estimated as the following: (I) first-line regimens: 10 and 14 days standard triple, 10 and 14 days sequential, 10 and 14 days concomitant non-bismuth quadruple, 14 days hybrid, (II) second-line salvage regimens: 10 and 14 days levofloxacin-containing triple regimens. Treatment costs using prototypes and/or generic drugs were calculated. Drug prices were collected and confirmed from two official online medical databases including all medicines approved by the Greek National Organization for Medicines. Regimens based on generics were more affordable than prototypes and those including pantoprazole yielded the lowest prices (mean: 27.84 €). Paradoxically, 10-day concomitant and 14-day hybrid regimens (currently providing good (90–94%) first-line eradication rates in Greece) cost the same (mean: 34.76 €). The expenditures for Hp eradication treatment regimens were estimated thoroughly for the first time in Greece. These data should be taken into account by Public Health policymakers both in Greece and the European Union, aiming for a better and less expensive therapeutic approach.