Background and objectives: Infections caused by resistant bacteria are a growing public health problem that is linked to many different causes, among them the antibiotics’ incorrect use plays an important role. According to the World Health Organization (WHO) the most dangerous behaviors are the early interruption of antibiotic therapy and the use of molecules without appropriate prescription. The authors conducted a systematic review to assess if antibiotic prescription with different regimens is connected to the onset of bacterial resistance. Methods: The authors performed an electronic and manual literature search on four databases (Web of Science, Scopus, PubMed, and Cochrane Register of Controlled Trials) from their inception to 15 June 2019. The date of the last search was 27 November 2019. Any article comparing cultural or genic analysis of resistance in patients that took antibiotics with at least two different regimens was included. No language restrictions were applied. Risk of bias for randomized controlled trials (RCTs) was assessed using the Cochrane collaboration’s tool whereas case-control and cohort studies were evaluated through the Newcastle–Ottawa scale. Results: The initial search resulted in a total of 1744 titles. After careful evaluation of all results, only three studies satisfied the outcome of the present review. From the qualitative analysis of data, it emerges that even if antibiotics are administered for a shorter period than the conventional one the species that inhabit the oral cavity can adapt quickly and express genes of antibiotic resistance. Additional evidence from this analysis is that not only does the proportion of resistant bacteria increase in the oral cavity, but also in more distant districts such as the intestine. Conclusions: Despite the great number of studies retrieved by electronic databases only few studies investigated the target of this review. The reason for this evidence is that it is not ethical to investigate and compare different antibiotic regimens, shorter or longer than the appropriate one. This evidence is applicable both to prophylactic administrations and to those aimed at treating infections. Besides this, the WHO affirms that, in the absence of infective complications, the prescription of antibiotic after every type of surgical intervention cannot be admitted and that studies dealing with antibiotic regimens that do not comply with drug’s pharmacodynamics characteristics cannot be ethically admitted. PROSPERO acknowledgement of receipt .