The 2016 fire blight epidemic in northern New York led to $16 million damage and significant tree losses in high-density orchards. Part of the destructive effects of fire blight relate to canker formation on apple wood, usually originating from shoot blight symptoms. To reduce or prevent shoot blight severity, we evaluated 12 post-infection spray programs on mature ‘Royal Cort’ trees after the artificial inoculation of shoots with Erwinia amylovora, using prohexadione-calcium (PCA) alone or combined with acibenzolar-S-methyl (ASM) sprayed dilute to drip, in an experiment repeated annually for two years. The greatest reduction of shoot blight severity, of a 72.5 and 78.8%, in the first and second year, respectively, was achieved with the highest PCA rate (247.1 mg/L) applied twice, 14 days apart, followed by the same treatment, but applied once (53.5 and 89.5%). The greatest control of canker initiation on perennial wood was achieved with a single 247.1 mg/L PCA application which reduced canker initiation for 71.5% the first year and a 100% in the second year. Three applications of 123.6 mg/L PCA + 25 mg/L ASM, each 14 days apart, reduced canker initiation a 78.6 and 83.5% on years 1 and 2, respectively. As cankers can kill dwarf trees, serve as inoculum source and overwintering reservoirs for the pathogen, our most effective post-infection programs might help in reducing or preventing canker development, thus minimizing tree losses after fire blight outbreaks.