In recent years, polymeric materials have become the dominant type of material used for drinking water pipe distribution systems. They have some advantages over other types of pipes such as cast iron, ductile iron, concrete, and copper. There are also concerns on the effect of polymeric pipes on water quality. The effect of polymeric pipes on desalinated water is an area that has not been significantly investigated in previous studies. The UAE is predominantly using a desalination plant in order to provide the water for the residents and industries. The purpose of this research was to investigate the effect of the combination of polymeric pipes and desalinated water on the formation of a disinfection byproduct. Three pipe loop systems were designed using polyvinyl chloride (PVC), polyethylene (PE), and polypropylene (PPR) materials to study the effect of polymeric pipes on trihalomethanes (THMs) formation. Natural organic matter (NOM) was used as a precursor for THMs. Experiments were conducted with different combinations of initial total organic carbon and initial calcium hypochlorite to study the effect of these operational parameters on the THM formation potential of the designed loop systems. The results of the experiments showed that PVC pipes have the most potential formation of THMs followed by PE and PPR pipes, respectively. High levels of bromide could shift the distribution of THMs by increasing the formation of brominated THMs. A statistical analysis of the obtained results showed that initial calcium hypochlorite has a significant effect on the formation of THMs. Initial total organic carbon (TOC) had the same effect; however, it did not have that strong correlation with THM formation like calcium hypochlorite.