Background The objective of this study was to determine the prevalence of plasmid-mediated AmpC (pAmpC) among Enterobacteriaceae isolated from humans and from retail meat in Egypt. Methods Enterobacteriaceae were isolated from patients with suspected bloodstream infection, human fecal samples, retail chicken meat samples and retail sheep meat samples. All group I Enterobacteriaceae were analyzed for presence of pAmpC genes by PCR. Antibiotic susceptibility testing was performed in all pAmpC positive isolates, followed by phenotypic and genotypic ESBL and carbapenemase testing on indication. Results The prevalence of pAmpC among group I Enterobacteriaceae isolated from 225 patients with bloodstream infection was 5.6% [95%CI 2.2–13.4]. Among 100 patients with community-onset gastroenteritis the prevalence in fecal samples was 4.8% [95%CI 2.1–10.7]. The prevalence among 112 chicken carcasses and 100 sheep meat samples was 2.4% [95%CI 0.7–8.4] and 1.1% [95%CI 0.2–5.7], respectively. In half of the AmpC positive isolates we detected an ESBL gene and 2 isolates harbored a carbapenemase gene. In five isolates there was resistance to at least three important alternative antibiotic drugs. Conclusions We consider the prevalence of pAmpC in Egypt, as found in our study, moderately low. To follow future trends in prevalence of pAmpC worldwide, a standardized screening algorithm for the detection of pAmpC is needed.