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Plasmid profile of multidrug resistant Helicobacter pylori isolated from ulcer patients in Ondo State, Nigeria was investigated. It was observed that the H. pylori isolated from ulcer patients in the course of the research were resistance to certain antibiotics. Consequently on the emergence of multiple drug resistance exhibited by the H. pylori, a total of 9 different antibiotics were tested against the H. pylori isolated from various locations to determine their in-vitro susceptibility pattern. The findings of the in-vitro antibiotics susceptibility testing are quite astonishing due to a high incidence of multiple drug resistance. Majority of the H. pylori showed high level of resistance against some specific number of antibiotics. The multidrug resistance observed in this study seems to be plasmid mediated. Moreover frequent use of over-the-counter antibiotics and abuse of non steroidal anti inflammatory drugs (NSAIDs) administration and abuse of drugs of sub – standard chemical quality has been identified as a major problem. The results from this investigative study have shown that resistance in H. pylori was plasmid based.