Improving the use of bioctechnological and classical plant resistance for herbivore pest control with less reliance on chemicals critically depends on predictable interactions with secondary pests. Performance of the potato aphid Macrosiphum euphorbiae (Thomas), a secondary pest of potato in eastern North America, was studied on potato, Solanum tuberosum L., lines with traits of potential resistance to primary pests. The lines tested were ‘Newleaf’, a transgenic ‘Superior’ cultivar expressing the Bacillus thuringiensis Berliner CryIIIA toxin, which is highly resistant to the Colorado potato beetle, Leptinotarsa decemlineata (Say); a transgenic ‘Kennebec’ cultivar expressing rice cystatin I, a protease inhibitor previously shown to inhibit cathepsin like digestive enzymes in the Colorado potato beetle; NYL 235–4, a potato derived by selective breeding following hybridization with S. berthaulthii, with a moderate density of glandular trichomes providing resistance to small insects by contact; and the commercial cultivars Superior and Kennebec used as controls. Transgenic Superior potatoes negatively affected M. euphorbiae’s growth and fecundity, in contrast with the OCI potato, which improved aphid performance. The flight incidence of young alatae of M. euphorbiae that completed development on transgenic Superior was significantly higher than in aphids from other potato lines. Aphid resistance in the ‘NYL 235–4’ line was complex and depended on aphid access being limited to leaves, which reduced survival and fecundity. However, when aphids had access to whole NYL 235–4 plants, aphid performance was restored, as they preferentially fed and reproduced on NYL 235–4 stems and apical buds of unfolding leaflets. The results illustrate that the performance of a secondary pest of potato can vary unpredictably, depending on the nature of the resistance factors involved in developing specific resistance to a primary pest.