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Background African animal trypanosomosis (AAT), transmitted by tsetse flies and tick-borne diseases are the main constraints to livestock production in sub-Saharan Africa. Vector control methods such as pour-on offer individual protection against ticks but not against tsetse so far, for which protection has always been communal, through a reduction of their density. The latter requires the treatment of a large part of the herd in a given landscape and is not instantaneous. Methodology/Principal Findings Two prospective surveys were conducted to evaluate the efficacy and persistence of a pour-on formulation composed of cypermetrhin, chlorpyrifos, piperonyl butoxid and citronella (Vectoclor, CEVA Santé Animal). In experimental conditions, tsetse flies were exposed to treated and control cattle. Flies knockdown and engorgement rates were determined and the product persistence was assessed as the time for these parameters to drop below 50% (T50). T50 was 37 days (95%CI: [33–41] days) and 46 days (95%CI: [39–56] days) for the knockdown and engorgement rates respectively. In field conditions, two cattle herds were monitored following a case-control experimental design, in the Adamaoua region of Cameroon. One herd was treated once with Vectoclor pour-on (treated group) and the second used as a control group (not treated). Ticks infestation rate, trypanosomosis prevalence and packed-cell volume were measured over the two months following treatment. The treatment was highly effective against ticks with a complete elimination three days after application in the treated group. Trypanosomosis prevalence was also significantly reduced during the study (by 4, P, Author Summary In sub-Saharan Africa, tsetse and tick borne disease are the main constraints to livestock production. Providing farmers effective products to control animal pests is a challenging task in the context of increasing resistance to insecticide in many vectors and reduction of available insecticide molecules. Moreover, the spread of invasive species of high economic importance such as the tick Rhipicephalus microplus stress the development of new tools. In this study, we evaluated the protective effect of a new pour-on formulation against tsetse, trypanosomosis and ticks in experimental and field trials. This product based on a mix of two insecticides, a repellent and a synergist prove to be very effective with an immediate effect on ticks and tsetse and low treatment frequency to maintain a low ticks infestation and trypanosomosis prevalence. This new insecticide formulation represents an important innovation in the field of vector control, offering a partial individual protection in addition to a collective control method against trypanosomosis vectors and ticks.