Compositional analysis is an important component of an integrated comparative approach to assessing the food and feed safety of new crops developed using biotechnology. As part of the safety assessment of cassava brown streak disease resistant 4046 cassava, a comprehensive assessment of proximates, minerals, amino acids, fatty acids, vitamins, anti-nutrients, and secondary metabolites was performed on leaf and storage root samples of 4046 cassava and its nontransgenic parental control, TME 204, collected from confined field trials in Kenya and Uganda over two successive cropping cycles. Among the 100 compositional components that were assessed in samples of 4046 and control TME 204 cassava roots (47 components) and leaves (53 components), there were no nutritionally relevant differences noted. Although there were statistically significant differences between the transgenic and control samples for some parameters, in most cases the magnitudes of these differences were small ( < 20%), and in every case where comparative literature data were available, the mean values for 4046 and control cassava samples were within the range of normal variation reported for the compositional component in question. Overall, no consistent patterns emerged to suggest that biologically meaningful adverse changes in the composition or nutritive value of the leaves or storage roots occurred as an unintended or unexpected consequence of the genetic modification resulting in 4046 cassava. The data presented here provide convincing evidence of the safety of 4046 cassava with respect to its biochemical composition for food and feed, and it could be considered as safe as its non-transgenic control.