Prohexadione-calcium (P-Ca) is widely used to reduce vegetative growth and labour costs associated with manual pruning. Orchard studies were conducted in 2012 and 2013 to determine the response of mature ‘Empire’/M.26 apple trees to individual or combined applications of P-Ca, ethephon (ETH), trinexapac-ethyl (TE), and maleic hydrazide (MH). Sprays were repeated three times at approximately 2-wk intervals starting at petal fall. All compounds reduced extension shoot growth, ranging from 40%–73% in 2012 and 26%–57% in 2013, relative to untreated controls. The greatest reduction in growth was achieved with ETH in one year and P-Ca ETH and MH in another. The tank-mixed combination of P-Ca ETH improved vegetative control compared with each compound applied alone. MH caused foliar phytotoxicity and damage to the apical meristem, resulting in the stimulation of lateral shoot growth. Reduction in shoot growth from any of the plant bioregulators (PBR) did not reduce dormant pruning times in the spring following application. Total and marketable fruit yield was unaffected by the PBRs, although applications of MH resulted in a significantly higher number of fruit per tree and crop load but a lower mean fruit weight and percent marketable fruit.