This paper investigates the effect of NPK fertilizer and poultry manure on the yield of cassava using 22 factorial design. A result of a field experiment conducted in the 2011/2012 planting season was collected from NIHORT, Ibadan. Under the sole cropping system, the analysis carried out revealed that the two levels of factor A (NPK fertilizer) are not significantly different in their contribution to cassava yield and so is their interaction effect. The two levels of the second factor (poultry manure) are found to be significantly different in their contribution to cassava yield. Under inter-cropping system, the different levels of factor B differs significantly in their contribution to cassava yield and also the interaction effect was found to be significant but the different levels of factor A do not differ significantly in their contribution to cassava yield.