We used molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) to evaluate the impact of mass drug administration (MDA) in sentinel locations in Egypt with high (11.5%) and low (4.1%) baseline microfilaria prevalence rates. Blood-fed Culex pipiens were pooled by household and tested for Wuchereria bancrofti DNA by PCR. There was no significant relationship between the infection status of household residents and parasite DNA status of mosquitoes from the same houses. After 5 MDA rounds, parasite DNA rates in mosquitoes in high- and low-prevalence areas were reduced by 93.8% and 100% to 0.19% (95% CI: 0.076-0.382%) and 0% (95% CI: 0-0.045%), respectively. These changes were consistent with decreases in microfilaria prevalence rates in these sites; they provide insight regarding the minimal mosquito DNA rates necessary for sustained transmission of filariasis in Egypt. We conclude that MX is a powerful tool for monitoring the impact of MDA on filariasis endemicity and transmission.