The standard practice of two or three preemptive insecticide applications at the start of pinhead (1–2-mm-diameter) squaring followed by threshold-triggered (when 10% of randomly selected squares have oviposition punctures) insecticide applications for boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), control does not provide reliable protection of cotton, Gossypium hirsutum L., lint production. This study, conducted during 2004 and 2005, showed that three to six fewer spray applications in a “proactive” approach, in which spraying began at the start of large (5.5–8-mm-diameter) square formation and continued at ≈7-d intervals while large squares were abundant, resulted in fewer infested squares and 1.4- to 1.7-fold more lint than the standard treatment. Fewer sprays and increased yield made proactive spraying significantly more profitable than the standard approach, which resulted in relatively low or negative economic returns. Harvest at 75% boll-split in the proactive spray regime of 2005 resulted in four-fold greater economic return than cotton harvested at 40% boll-split because of improved protection of large squares and the elimination of late-season sprays inherent to standard spray regime despite the cost of an extra irrigation in the 75% boll-split treatments. The earlier, 40% harvest trigger does not avoid high late-season boll weevil pressure, which exerts less impact on bolls, the predominant form of fruiting body at that time, than on squares. Proactive spraying and harvest timing are based on an important relationship between nutrition, boll weevil reproduction, and economic inputs; therefore, the tactic of combining proaction with harvest at 75% boll-split is applicable where boll weevils are problematic regardless of climate or region, or whether an eradication program is ongoing.