The present study examined the effects of exercise utilising traditional resistance training (leg press) or ‘cardio’ exercise (recumbent cycle ergometry) modalities upon acute physiological responses. Nine healthy males underwent a within session randomised crossover design where they completed both the leg press and recumbent cycle ergometer conditions. Conditions were approximately matched for effort and duration (leg press: 4 × 12RM using a 2 s concentric and 3 s eccentric repetition duration controlled with a metronome, thus each set lasted 60 s; recumbent cycle ergometer: 4 × 60 s bouts using a resistance level permitting 80–100 rpm but culminating with being unable to sustain the minimum cadence for the final 5–10 s). Measurements included VO2, respiratory exchange ratio (RER), blood lactate, energy expenditure, muscle swelling, and electromyography. Perceived effort was similar between conditions and thus both were well matched with respect to effort. There were no significant effects by ‘condition’ in any of the physiological responses examined (all p > 0.05). The present study shows that, when both effort and duration are matched, resistance training (leg press) and ‘cardio’ exercise (recumbent cycle ergometry) may produce largely similar responses in VO2, RER, blood lactate, energy expenditure, muscle swelling, and electromyography. It therefore seems reasonable to suggest that both may offer a similar stimulus to produce chronic physiological adaptations in outcomes such as cardiorespiratory fitness, strength, and hypertrophy. Future work should look to both replicate the study conducted here with respect to the same, and additional physiological measures, and rigorously test the comparative efficacy of effort and duration matched exercise of differing modalities with respect to chronic improvements in physiological fitness.