Background The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness ($\dot{V}{O}_{2\text{peak}}$) and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) have different effects on $\dot{V}{O}_{2\text{peak}}$ and 6-minute walk distance (6MWD). Methods and Results In this 24-week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT). MICT trained to target intensity at the ventilatory anaerobic threshold. HIIT trained at the maximal tolerable treadmill speed/grade using a novel program of 2 work-to-recovery protocols: 30:60 and 120:180 seconds. V̇O₂ and heart rate was measured during performance of the exercise that was prescribed at 8 and 24 weeks for treatment fidelity. Main outcomes were change in $\dot{V}{O}_{2\text{peak}}$ and 6MWD. Assessors were blinded to the treatment group for $\dot{V}{O}_{2\text{peak}}$ but not 6MWD. Secondary outcomes were change in ventilatory anaerobic threshold, cognition, gait-economy, 10-meter gait-velocity, balance, stair-climb performance, strength, and quality-of-life. Among 47 participants randomized to either MICT (n=23) or HIIT (n=24) (mean age, 62±11 years; 81% men), 96% completed training. In intention-to-treat analysis, change in $\dot{V}{O}_{2\text{peak}}$ for MICT versus HIIT was 2.4±2.7 versus 5.7±3.1 mL·kg^-1·min^-1 (mean difference, 3.2 [95% CI, 1.5-4.8]; P<0.001), and change in 6MWD was 70.9±44.3 versus 83.4±53.6 m (mean difference, 12.5 [95% CI, -17 to 42]; P=0.401). HIIT had greater improvement in ventilatory anaerobic threshold (mean difference, 2.07 mL·kg^-1·min^-1 [95% CI, 0.59-3.6]; P=0.008). No other between-group differences were observed. During V̇O₂ monitoring at 8 and 24 weeks, MICT reached 84±14% to 87±18% of $\dot{V}{O}_{2\text{peak}}$ while HIIT reached 101±22% to 112±14% of $\dot{V}{O}_{2\text{peak}}$ (during peak bouts). Conclusions HIIT resulted in more than a 2-fold greater and clinically important change in $\dot{V}{O}_{2\text{peak}}$ than MICT. Training to target (ventilatory anaerobic threshold) during MICT resulted in ~3 times the minimal clinically important difference in 6MWD, which was similar to HIIT. These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional MICT in appropriately screened individuals. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03006731.