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Exercise training regimes can lead to improvements in measures of cardiorespiratory fitness (CRF), improved general health, and reduced morbidity and overall mortality risk. High-intensity interval training (HIIT) offers a time-efficient approach to improve CRF in healthy individuals, but the relative benefits of HIIT compared with traditional training methods are unknown in across different disease cohorts.This systematic review and meta-analysis compares CRF gains in randomized controlled trials of short-term (<8 wk) HIIT versus either no exercise control (CON) or moderate continuous training (MCT) within diseased cohorts. Literature searches of the following databases were performed: MEDLINE, EMBASE, CINAHL, AMED, and PubMed (all from inception to December 1, 2017), with further searches of Clinicaltrials.gov and citations via Google Scholar. Primary outcomes were effect on CRF variables: V˙O2peak and anaerobic threshold.Thirty-nine studies met the inclusion criteria. HIIT resulted in a clinically significant increase in V˙O2peak compared with CON (mean difference [MD] = 3.32 mL·kg−1·min−1, 95% confidence interval [CI] = 2.56–2.08). Overall HIIT provided added benefit to V˙O2peak over MCT (MD = 0.79 mL·kg−1·min−1, 95% CI = 0.20–1.39). The benefit of HIIT was most marked in patients with cardiovascular disease when compared with MCT (V˙O2peak: MD = 1.66 mL·kg−1·min−1, 95% CI = 0.60–2.73; anaerobic threshold: MD = 1.61 mL·kg−1·min−1, 95% CI = 0.33–2.90).HIIT elicits improvements in objective measures of CRF within 8 wk in diseased cohorts compared with no intervention. When compared with MCT, HIIT imparts statistically significant additional improvements in measures of CRF, with clinically important additional improvements in V˙O2peak in cardiovascular patients. Comparative efficacy of HIIT versus MCT combined with an often reduced time commitment may warrant HIIT’s promotion as a viable clinical exercise intervention.