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Background\ud Despite the progress achieved in scaling-up mass drug administration (MDA) for lymphatic filariasis (LF) in Ghana, communities with persistent LF still exist despite over 10 years of community treatment. To understand the reasons for persistence, we conducted a study to assess the status of disease elimination and understand the adherence to interventions including MDA and insecticide treated nets.\ud Methodology and principal findings\ud We conducted a parasitological and epidemiological cross-sectional study in adults from eight villages still under MDA in the Northern Region savannah and the coastal Western Region of the country. Prevalence of filarial antigen ranged 0 to 32.4% and in five villages the prevalence of night blood microfilaria (mf) was above 1%, ranging from 0 to 5.7%. Median mf density was 67 mf/ml (range: 10-3,560). LF antigen positivity was positively associated with male sex but negatively associated with participating in MDA the previous year. Male sex was also associated with a decreased probability of participating in MDA. A stochastic model (TRANSFIL) was used to assess the expected microfilaria prevalence under different MDA coverage scenarios using historical data on one community in the Western Region. In this example, the model simulations suggested that the slow decline in mf prevalence is what we would expect given high baseline prevalence and a high correlation between MDA adherence from year to year, despite high MDA coverage. \ud Conclusions\ud There is a need for an integrated quantitative and qualitative research approach to identify the variations in prevalence, associated risk factors and intervention coverage and use levels between and within regions and districts. Such knowledge will help target resources and enhance surveillance to the communities most at risk and to reach the 2020 LF elimination goals in Ghana.