Excessive vine growth in sweetpotato has been associated with lower storage root yield. Prohexadione–calcium (Pro-Ca), a plant growth retardant, has been used to reduce vegetative growth and increase harvest efficiency and yield in many fruit and row crops. The influence of Pro-Ca on sweetpotato (Ipomoea batatas Lam.) vegetative growth and storage root yield was evaluated in this study. In 2010 and 2011, the sweetpotato cvs. Beauregard, Porto Rico, O’ Henry, and SC1149-19 were sprayed with 0 and 810 mg a.i./L Pro-Ca in a split plot randomized complete block. Each plot received two sprays, the first at 2 weeks after transplanting and the second at 6 weeks after transplanting. When averaged across cultivars, Pro-Ca significantly (P ≤ 0.05) reduced vine length and vine yield and increased total root yield compared with the control. There was no significant Pro-Ca × cultivar interaction on any trait. Total biomass was not significantly (P ≤ 0.05) different between Pro-Ca-treated and control plants. However, the treated plants had more total root yield, whereas the control plants had more vine yield, suggesting that Pro-Ca treatment affected the distribution of assimilates. Data from this study suggested that it may be possible to use Pro-Ca to manipulate the source-sink relationship for higher storage root yield in sweetpotato.