This study was designed to identify the effects of variable concentrations of chloride on microbial regrowth, disinfection efficacy, and metal release in drinking water distribution systems. Annular reactors (ARs) containing cast iron or polycarbonate coupons were operated in this study to simulate distribution systems. Experiments were conducted with test water containing chloride concentrations of 10, 75, and 250 mg/L. Chlorine disinfection was applied to achieve 0.2 and 1.0 mg/L free chlorine residuals. Results showed that the ARs operated with elevated chloride concentrations were not significantly different from the ARs operated with low chloride concentrations in terms of microbial regrowth. However, there was a significant increase in iron concentrations after chlorination in the high chloride ARs. Further, more iron release was observed in these ARs at 1.0 mg/L compared to 0.2 mg/L chlorine residual. Higher chlorine doses were required to achieve goal residuals for those ARs with higher chloride concentration in cast iron systems. However, in polycarbonate systems, similar doses of chlorine were required to achieve the target free chlorine residual in both low-chloride and high-chloride ARs.