The effect of feeding spray-dried plasma (SDP) during the starter period was evaluated with a commercial broiler integrator on performance and overall health of broilers. The I See Inside (ISI) methodology assessing gut health in broilers was used as a tool to evaluate the impact of dietary interventions under commercial conditions. One hundred farms with approximately 1.1 million broilers were used at a Brazilian broiler integrator. Two groups of farms were fed either a control or an SDP diet containing 1% SDP, from 0 to 10 d of age. Diets were formulated to have similar nutritional density, containing zinc bacitracin and CuSO4 from 0 to 28 d. After 10 d, both groups were fed common commercial diets. Performance data were analyzed together or by type of ventilation system: positive pressure or negative pressure. Birds were sent to market as they reached 3.05 kg; therefore, age at slaughter (AS) was evaluated as a dependent variable along with other performance measures. From the 100 farms in the trial, 35 (16 control and 19 SDP farms) were selected for the assessment of broilers health, biosecurity, and local management. For that, 6 broilers per farm at 14 ± 2 d of age were necropsied and ileum sampled for the ISI methodology evaluation. Biosecurity and management were also evaluated to obtain the influence of those parameters on animal health. SDP-fed birds demonstrated improved feed conversion ratio, reduced mortality, and 1 d less for AS (P < 0.05) vs. control group (P < 0.05) regardless of the type of ventilation. During necropsy, birds fed SDP showed lower coccidiosis and locomotor system lesions as the overall ISI score compared to controls. Histologic intestinal alterations were also lower in SDP-fed broilers (P < 0.05). In conclusion, feeding 1% SDP in the starter period to broilers resulted in improved performance and health under both good and bad management and biosecurity standards independent of the type of ventilation. Overall, there was good agreement between the ISI method and performance improvements observed.