In this experimental study on a prototype lever-propelled wheelchair, the effect of a range of mechanical advantages (MA) on physical strain, oxygen uptake, energy cost, mechanical efficiency, stroke frequency and perceived exertion was examined. Nine out of 10 male nonwheelchair users successfully performed five submaximal tests on a motor-driven treadmill in a prototype bi-manual asynchronous lever-propelled tricycle. Each test contained the same protocol, but made use of one of the five different MAs. In every test the inclination level increased by 1% every third minute, starting on 0% up to 3%. The velocity was kept constant at 0.97 m.s-1. Variables measured included oxygen uptake, minute ventilation, respiratory exchange ratio, heart rate, and stroke frequency. Analysis for repeated measures was conducted on the main factors slope and MA and their interaction. Additional analysis include a multiple regression analysis. All statistics were conducted with a p < 0.05 level of significance. MA had a significant effect (p < 0.05) on oxygen uptake, energy cost, mechanical efficiency, and stroke frequency. These results suggest that the implementation of a range of MAs on a lever-propelled wheelchair may accommodate different external conditions (slope, climatic, surface conditions, sports, and recreational conditions) and different user groups more readily. This may improve the social radius of action and freedom of mobility of individuals confined to wheelchairs.