Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment is a limitation of using human surveys to provide an early indicator of the impact of mass drug administration (MDA), and MX may be more useful in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) in 35 primary sampling units (PSUs) in Samoa, and investigated associations between the presence of PCR-positive mosquitoes and Ag-positive humans. We observed a statistically significant decline in estimated mosquito infection prevalence post-MDA at the national level (from 0.9% to 0.3%, OR 0.4) but no change in human Ag prevalence during this time. Ag prevalence in 2019 was higher in randomly selected PSUs where PCR-positive pools were detected (1.4% in ages 5-9; 4.8% in ages ≥10), compared to those where PCR-positive pools were not detected (0.2% in ages 5-9; 3.2% in ages ≥10). Our study provides promising evidence for MX as a complement to human surveys in post-MDA surveillance.