The current standard practice of 2–3 pre-emptive insecticide applications at the start of pinhead (1–2-mm-diameter) squaring followed by threshold-triggered (whenever 10% of randomly selected squares have oviposition punctures) insecticide applications for boll weevil, Anthonomus grandis grandis Boheman, control does not provide a reliably positive impact on cotton, Gossypium hirsutum L., yields in subtropical conditions. This study showed that four fewer spray applications in a ‘proactive’ approach, where spraying began at the start of large (5.5–8-mm-diameter) square formation and continued at 7–8-d intervals while large squares were abundant, resulted in fewer infested squares and 46–56% more yield than the standard treatment at two locations during 2004. The combination of fewer sprays and increased yield made the proactive approach 115–130% more profitable than the standard. The proactive approach entails protection only at the crop’s most vulnerable stage (large squares) that, as a source of food, accelerates boll weevil reproduction. In contrast, the standard approach protects early-season small squares and later-season bolls, both of which contribute less to boll weevil reproduction than large squares. Proaction is an in-season crop protection approach that can be used to increase yield in individual fields during the same season, and could be incorporated into boll weevil eradication strategy that involves later diapause sprays. Because proaction is based on an important relationship between the cotton plant and boll weevil reproduction, the tactic will probably be effective regardless of climate or region.