Abstract Background Podoconiosis, or non-filarial elephantiasis, is a neglected tropical disease (NTD) characterised by swelling of the lower legs. When left untreated, this disfiguring condition has a significant social impact. This study aimed to describe the stigma experience among podoconiosis patients in Dembecha, Northern Ethiopia and assess potential associations between stigma and sociodemographic determinants. Methods The study was conducted in May 2012 in Northern Ethiopia. A questionnaire-based cross-sectional study design was used and stigma was assessed using a validated podoconiosis stigma scale including 'felt’ and 'enacted’ stigma domains. Enacted stigma includes the experience of discrimination such as abuse, loss of employment or prejudicial attitudes, while felt stigma is the perceived fear of enacted stigma. A multivariable linear regression model was used to explore determinants that may be associated with stigma. Results A total of 346 clinically confirmed podoconiosis patients participated in the study. The total mean score of all stigma scale items was 30.7 (Range = 0 to 96). There was a higher mean score of scale items in domains of felt stigma (21.7; Range = 0 to 45) as compared to enacted stigma (9.0; Range = 0 to 51). The total mean score of all stigma scale items appeared to increase with disease stage. A final adjusted linear regression model found an association between stigma and factors including monthly income, duration lived in the current residence, and disease stage, after controlling for confounders. Conclusion Podoconiosis is a stigmatized disease with a clear social impact. This paper documented the burden of podoconiosis-related stigma and identified associated factors. Programs aimed at preventing and treating podoconiosis should incorporate interventions to mitigate both felt and enacted stigma. Interventions targeting patients should prioritize those with advanced disease.