Tithonia diversifolia is widely used in African traditional medicine for the treatment of a large number of ailments and disorders, including malaria. In the present study, we evaluated the repellent activity of essential oils (EO) of this plant against Anopheles coluzzii, a major vector of malaria in Africa. Fresh leaves of T. diversifolia were used to extract EO, which were used to perform repellency assays in the laboratory and in the field using commercially available N,N-Diethyl-meta-toluamide (DEET) and Cymbopogon (C.) citratus EO as positive controls and vaseline as negative control. The repellency rates and durations of protection of the human volunteers involved were used as measures of repellent activity. Chemical composition of the T. diversifolia EO was established further by gas chromatography coupled with mass spectrometry. The moisture content and oil yield were 81% and 0.02% respectively. A total of 29 compounds in the T. diversifolia EO was identified, with d-limonene (20.1%), α-Copaene (10.3%) and o-Cymene (10.0%) as the most represented. In field studies, the mean time of protection against mosquito bites was significantly lower in T. diversifolia EO-treated volunteers compared to treatments with C. citratus EO (71 min versus 125 min, p = 0.04), but significantly higher when compared with the non-treated volunteers (71 min vs 0.5 min, p = 0.03). The same pattern was found in laboratory repellency assays against A. c oluzzii. In contrast, repulsion rates were statistically similar between T. diversifolia EO and positive controls. In conclusion, the study suggests promising repellent potential of leaves of T. diversifolia EO against A. coluzzii.