Intradialytic exercise (ID) programs are effective and safe for hemodialysis (HD) patients to avoid functional deterioration. However, exercise is not routinely undertaken in most HD units, and we do not know if home-based (HB) programs are as effective as ID programs. The purpose of this study was to compare the effects of 16 weeks of ID exercise versus a HB exercise program for HD patients. A total of 46 patients were randomly assigned to the ID group (n = 24) or HB group (n = 22). They completed a 16-week combined exercise program 3 times/week. We measured physical activity level, physical functioning, depression level, and health-related quality of life at baseline and after 16 weeks. A significant time effect was found in both groups for the physical activity level (p = 0.012). There was also a significant group-time interaction effect for the one-leg standing test (OLST) (p = 0.049) and a significant time effect for the Short Physical Performance Battery (p = 0.013), timed up-and-go test (p = 0.005), sit-to-stand-10 (p = 0.027), right and left hand handgrip (p = 0.044, p < 0.001), one-heel left leg raise (p = 0.019), and 6-minute walking (p = 0.006), depression (p = 0.017). HRQoL remained unchanged. There was no difference between the two interventions on the tested outcomes (besides OLST). Both interventions were associated with positive changes of the physical activity levels and physical function. Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) present a progressive functional deterioration, poor health-related quality of life (HRQoL), and low levels of physical activity compared to their healthy age-matched counterparts 1,2. In addition, this population often presents symptoms of depression and anxiety 3-5. Exercise programs for people with CKD have been implemented since the beginning of 1980s 6. For optimal benefits, these programs should include a combination of aerobic exercise and strength resistance 7. The few studies carried out in HD units in Spain have tested different exercise types including strength-resistance 8 , resistance 9 , low intensity endurance training 10,11 , neuromuscular electrostimulation 12,13 , and virtual reality 14. Different exercise modalities have been studied in the literature, but intradialytic (ID) exercise is considered the best approach 15 because adherence to this modality is higher than with other formats 16. Nevertheless, to the best of our knowledge, HD units in Spain do not currently include exercise as part of routine HD treatments, perhaps because of the financial cost associated with ID exercise programs. Thus, home-based (HB) programs