Multiple helminth infections are very common in communities of southern Laos. Preventive chemotherapy in combination with health education is the mainstay of control. We assessed the knowledge, perceptions and practices of rural communities related to endemic helminthiasis and their control during a mass drug administration (MDA) campaign. Short interviews with household heads (n = 192), direct observations and discussions with attendees of MDAs, and in-depth interviews with local opinion leaders (n = 21) were carried out. Quantitative and qualitative data analysis was performed. Results showed that opinion leaders and villagers were well aware of the importance of attending MDA. Leaders perceived the effectiveness of MDA against severe schistosomiasis and appreciated that it was provided for free and in their village. They encouraged villagers to attend it. Anticipated adverse events of praziquantel was a barrier for participation. A majority of leaders purchased deworming tablet (mebendazole, albendazole) in a local pharmacy for deworming when MDA is absent in their villages (19/21). Most leaders (20/21) had a good knowledge on severe schistosomiasis though only a few of them (5/21) described its cause correctly. They knew little about the disease consequences of liver fluke (3/21) and soil-transmitted helminth (4/21) infections but more about their causes. A high risk for worm infection was observed: consumption of raw or insufficiently cooked fish (100%), frequent physical contacts with Mekong River water (76.0%) and low number of latrines (14.5%). In conclusion, MDA is widely accepted in affected communities. Avoiding severe schistosomiasis was the main motivation to comply. Participation rates increased significantly with drugs provided free of charge in the villages. Better knowledge on the consequences of worm infections and on its modes of transmission will foster the distribution and acceptance of appropriate preventive treatment and other measures in helminth-endemic communities. Where multiple infections require several drugs for MDA, preceding health education and information about MDA and its benefits are a prior condition. (C) 2014 Elsevier B.V. All rights reserved.