The cotton aphid, Aphis gossypii is an economically significant insect pest infesting various important crops and vegetables. The neonicotinoid, acetamiprid was recommended against aphids with excellent results. Resistance emergence and environmental pollution makes acetamiprid a favorable alternative to conventional insecticides. The aims of the present work were to predict acetamiprid resistance risk in A. gossypii, investigate cross resistance to other tested insecticides and explore acetamiprid stability in the absence of selection. A field-collected population from Sharqia governorate, Egypt was selected with acetamiprid. After 16 generations of selection, there was a 22.55-fold increase in LC50 and the realized heritability (h2) of resistance was 0.17. Projected rates of resistance indicated that, if h2 = 0.17 and 50% of the population was killed at each generation, then a tenfold increase in LC50 would be expected in 12.2 generations. If h2 was 0.27 then 7.63 generations would be needed to achieve the same level. In contrast, with h2 of 0.07 it necessitates about 30 generations of selection to reach the same level. Cross resistance studies exhibited that the selected strain showed obvious cross resistance to the other tested neonicotinoid members, moderate cross resistance to alpha-cypermethrin and no cross resistance to pymetrozine. Fortunately, resistance to acetamiprid in the cotton aphid was unstable and resistance reverses the nearby susceptible strain throughout five generations without exposure to acetamiprid. Our results exhibited cotton aphid potential to develop resistance to acetamiprid under continuous selection pressure. The instability of acetamiprid makes A. gossypii amenable to resistance management tactics such as rotation with pymetrozine.