The mechanical work of breathing (Wb) is an insightful tool used to assess respiratory mechanics during exercise. There are several different methods used to calculate the Wb, however, each approach having its own distinct advantages/disadvantages. To date, a comprehensive assessment of the differences in the components of Wb between these methods is lacking. We therefore sought to compare the values of Wb during graded exercise as determined via the four most popular methods: 1) pressure-volume integration; 2) the Hedstrand diagram; 3) the Otis diagram; and the 4) modified Campbell diagram. Forty-two participants (30 ± 15 yr; 16 women) performed graded cycling to volitional exhaustion. Esophageal pressure-volume loops were obtained throughout exercise. These data were used to calculate the total Wb and, where possible, its subcomponents of inspiratory and expiratory, resistive and elastic Wb, using each of the four methods. Our results demonstrate that the components of Wb were indeed different between methods across the minute ventilations engendered by graded exercise. Importantly, however, no systematic pattern in these differences could be observed. Our findings indicate that the values of Wb obtained during exercise are uniquely determined by the specific method chosen to compute its value-no two methods yield identical results. Because there is currently no "gold-standard" for measuring the Wb, it is emphasized that future investigators be cognizant of the limitations incurred by their chosen method, such that observations made by others may be interpreted with greater context, and transparency.