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Cardiorespiratory fitness (CRF) is a key marker of health and performance, commonly assessed through treadmill running (TR). However, deep-water running (DWR) has emerged as an alternative modality, minimizing joint impact while preserving cardiovascular stimuli. Despite its potential, inconsistencies in CRF responses between TR and DWR remain unexplored in a systematic synthesis. To systematically review and compare the cardiorespiratory responses of maximal CRF tests performed in DWR and TR. This systematic review followed the PRISMA guidelines and was registered in PROSPERO (CRD42021260382). Searches were conducted in PubMed, Scielo, Embase, Scopus, and Web of Science, without publication date restrictions. Inclusion criteria encompassed studies assessing healthy adults (18–59 years) performing maximal CRF tests in both DWR and TR. Cardiorespiratory variables analyzed included VO₂max, heart rate (HR), pulmonary ventilation (VE), and respiratory exchange ratio (RER). Study quality was assessed using the TESTEX scale. Fourteen studies comprising 225 participants met the inclusion criteria. VO₂max values in DWR ranged from 76% to 90% of those observed in TR. HR, VE, and blood lactate accumulation were significantly lower in DWR, whereas perceived exertion remained similar. Differences were attributed to hydrostatic pressure, reduced activation of antigravity muscles, altered biomechanics, and enhanced thermoregulation. TR elicits higher cardiometabolic demands than DWR. While DWR is a submaximal alternative, its prescription should be based on aquatic-specific testing. Future studies should refine standardized protocols and investigate chronic adaptations.