Backround: Although "slash and clear" (slashing and clearing trailing vegetation where blackflies breed) has already proven its effectiveness in reducing blackfly densities in low transmission foci, the feasibility and impact of this strategy in very high transmission foci with large rivers and important vector densities is yet to be demonstrated. Objective: To evaluate the impact of "slash and clear" approach on blackfly densities and onchocerciasis transmission.  Methods: Two first-line villages (Bayomen used as control site and Biatsota used as intervention site) where selected in Centre Region of Cameroon. In each village, baseline data were collected for one year, using human landing catching method. Two days of ground and boat prospection was done, for the identification and characterization of blackflies breeding sites. The "slash and clear" was conducted once a month during nine months. Generalized estimating equations were used to evaluate the effect of intervention, adjusted on baseline data. Results: Prior to intervention, a total of 56870 and 51240 blackflies were collected in Bayomen and Biatsota, respectively. No significant difference was found between the two villages (p= 0.7545). The main attachment points for the blackfly larvae were the plant Pandanus candelabrum (˃90% of larvae/pupae). After the intervention (destruction of the blackfly habitat) period, blackfly densities declined from 51240 to 25520 in the intervention site (50.2% reduction) while in the control site, the densities declined from 56870 to 49471 (13% reduction); the observed reduction was significantly more important in the intervention site compared to the control site (p=0.0213). Conclusions: This study revealed that the "slash and clear" approach has a significant impact on vector densities in a very high transmission setting. Additional studies are needed to investigate the long-term impact of the "slash and clear" strategy, and how it can be used to supplement mass drug administration to accelerate the onchocerciasis elimination.