A mixture of C8/C10 fatty acid methyl esters (FAME) when applied directly and exclusively to leaf axils of greenhouse-grown tomato (Lycopersicon esculentum Mill.) significantly inhibited side shoot development. Plants grown in a single cluster production system in winter produced 8.9 side shoots/plant, whereas those treated with C8/C10 FAME 45 days after sowing, produced only 0.7 side shoots/plant. Total pruning weight of the side shoots was reduced from 40.2 g/plant to 1.3 g/plant. Fruit yield increased 14% with C8/C10 FAME treatment and there was an increase in the harvest index from 0.63 to 0.70. For a spring crop, in which average daily irradiance was more than twice that in winter, overall yield increased 70% when compared to the winter crop. As in winter, side shoot number and side shoot weight/plant were significantly reduced by C8/C10 FAME, but there was no difference in crop yield between C8/C10 FAME and untreated plants. In both winter and spring, untreated plants required hand pruning three times during the production period, whereas C8/C10 FAME-treated plants were pruned only once at the time of application. A C8/C10 free fatty acid (FA) mixture was also applied to one and two-cluster plants with similar results. In the multiple cluster system, application of the C8/C10 FA mixture instead of side shoot pruning reduced plant height and increased yield from 6.4 to 7.4 kg/plant. C8/C10 FA or C8/C10 FAME treatment could be a useful labor saving strategy in greenhouse tomato production and may increase crop yield under conditions in which assimilates may be limited by environmental factors, or as a result of a high level of competition from other fruits or shoots.