Background: Tsetse flies are the sole vectors of human and animal trypanosomosis. In Burkina Faso, a project aiming to create zones free of tsetse flies and trypanosomosis was executed from June 2006 to December 2013. After the determination of tsetse distribution in the intervention area from December 2007 to November 2008, the control campaign was launched in November 2009 and ended in December 2013. The goal was to eliminate tsetse flies from 40,000 km(2) of area, through an integrated control campaign including insecticide targets, traps and cattle, sequential aerial treatment (SAT) and the mass treatment of livestock using trypanocides. The campaign involved assistance of the beneficiary communities at all the steps of the control strategy with insecticide impregnated targets. Methods: This study was carried out to assess the impact of the control project on tsetse apparent density per trap per day (ADT). To evaluate the effectiveness of tsetse control, 201 sites were selected based on the baseline survey results carried out from December 2007 to November 2008. These sites were monitored bi-monthly from January 2010 to November 2012. At the end-of-study in 2013 a generalized entomological survey was carried out in 401 infested sites found during the longitudinal survey done before the control. Barrier and tsetse persistence areas were treated by ground spraying and evaluated. Controls were also done before and after aerial spraying. Results: In the insecticide-impregnated target area, the control showed that ADT of tsetse flies declined from 10.73 (SD 13.27) to 0.43 (SD 2.51) fly/trap/day from the third month of campaign onwards (P < 0.0001) and remained low thereafter. At the end of the campaign in 2013, an 83% reduction of ADT was observed for Glossina palpalis gambiensis and a 92% reduction for G. tachinoides. Tsetse flies were captured only in 29% of the sites found infested in 2008. Conclusions: Tsetse flies could be suppressed efficiently but their elimination from the targeted area may require the use integrated methods including the Sterile Insect Technique, which is programmed through the development of the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC Burkina) insectarium. The challenge will remain the sustainability of the achievement.