Background: An integrated strategy of intervention against tsetse flies was implemented in the Upper West Region of Ghana (9.62u-11.00u N, 1.40u-2.76u W), covering an area of <18,000 km2 within the framework of the Pan-African Tsetse and Trypanosomosis Eradication Campaign. Two species were targeted: Glossina tachinoides and Glossina palpalis gambiensis. Methodology/Principal Findings: The objectives were to test the potentiality of the sequential aerosol technique (SAT) to eliminate riverine tsetse species in a challenging subsection (dense tree canopy and high tsetse densities) of the total sprayed area (6,745 km2) and the subsequent efficacy of an integrated strategy including ground spraying (<100 km2), insecticide treated targets (20,000) and insecticide treated cattle (45,000) in sustaining the results of tsetse suppression in the whole intervention area. The aerial application of low-dosage deltamethrin aerosols (0.33-0.35 g a.i/ha) was conducted along the three main rivers using five custom designed fixed-wings Turbo thrush aircraft. The impact of SAT on tsetse densities was monitored using 30 biconical traps deployed from two weeks before until two weeks after the operations. Results of the SAT monitoring indicated an overall reduction rate of 98% (from a pre-intervention mean apparent density per trap per day (ADT) of 16.7 to 0.3 at the end of the fourth and last cycle). One year after the SAT operations, a second survey using 200 biconical traps set in 20 sites during 3 weeks was conducted throughout the intervention area to measure the impact of the integrated control strategy. Both target species were still detected, albeit at very low densities (ADT of 0.27 inside sprayed blocks and 0.10 outside sprayed blocks). Conclusions/Significance: The SAT operations failed to achieve elimination in the monitored section, but the subsequent integrated strategy maintained high levels of suppression throughout the intervention area, which will contribute to i