Tomato spotted wilt virus (TSWV) has become the most serious problem in flue-cured tobacco in Georgia and is a growing problem in other tobacco-growing areas in the United States. The effects of transplant age (6 to 10 weeks), tobacco cultivar (K-326 and NC-71), and preplant applications of acibenzolar-S-methyl (ASM) and the insecticide imidacloprid (IMD) were evaluated on levels of TSWV infection, number of symptomatic plants, and yield in field trials over 4 years. In all 4 years and in four of five trials, treatment of transplants with ASM and IMD resulted in fewer symptomatic plants, smaller areas under the disease progress curve (AUDPC), and higher yields compared with the nontreated controls. There were no consistent effects of transplant age or cultivar on number of symptomatic plants or systemic infections, AUDPC, or yield. Treatment of transplants with ASM and IMD can significantly reduce the number of symptomatic plants in the field and substantially increase yields and value per hectare.