The modified Campbell diagram provides one of the most comprehensive assessments of the work of breathing (Wb) during exercise, wherein the resistive and elastic work of inspiration and expiration are quantified. Importantly, a necessary step in constructing the modified Campbell diagram is to obtain a value for chest wall compliance (CCW). To date, it remains unknown whether estimating or directly measuring CCW impacts the Wb, as determined by the modified Campbell diagram. Therefore, the purpose of this study was to evaluate whether the components of the Wb differ when the modified Campbell diagram is constructed using an estimated versus measured value of CCW. Forty-two participants (n = 26 men, 16 women) performed graded exercise to volitional exhaustion on a cycle ergometer. CCW was measured directly at rest via quasistatic relaxation. Estimated values of CCW were taken from prior literature. The measured value of CCW was greater than that obtained via estimation (214 ± 52 mL/cmH2O vs. 189 ± 18 mL/cmH2O; P < 0.05). At modest-to-high minute ventilations (i.e., 50-200 L/min), the inspiratory elastic Wb was greater and expiratory resistive Wb was lower, when modified Campbell diagrams were constructed using estimated compared with measured values of CCW (P = 0.001). These differences were however small and never exceeded ±5%. Thus, although our findings demonstrate that estimating CCW has a measurable impact on the determination of the Wb, its effect appears relatively small within a cohort of healthy adults during graded exercise.