<b><i>Background:</i></b> We compared myocardial perfusion in patients first on conventional hemodialysis (HD) and then on hemodiafiltration (HDF). <b><i>Methods:</i></b> Myocardial perfusion scintigraphy was performed in 25 patients pre- and post-HD. Patients were then converted to HDF for 3 months prior to repeating the scintigraphy. ^99mTc-methoxyisobutylisonitrile was administered intravenously pre-dialysis and then within the last hour of dialysis. Up to 90 min after injection, tomographic images were obtained. Clinical and laboratory data were collected pre- and post-dialysis. <b><i>Results:</i></b> Five patients did not complete the study. Patients entering the study were on average 41.7 years old and on HD for 4 years (median). The mean standard Kt/V for the two procedures was not statistically different (1.55 for HD and 1.48 for HDF). The mean substitution volume for HDF was 18.48 liters. There were no significant differences in changes in blood pressures between HD and HDF (p = 0.22). There were no significant differences in myocardial perfusion defects in patients on HD compared with those on HDF. During dialysis in both studies, the data showed a general trend to worsening of perfusion defects. <b><i>Conclusions:</i></b> There was no advantage of HDF over HD with no statistical difference in perfusion defects between HD and HDF. There was a trend to worsening of perfusion defects during dialysis in the majority on HD and HDF. Midweek dialysis perfusion scores appeared to be consistently lower than early-week dialysis, but this was not statistically significant. The pathogenesis of the defects may lie at a microcirculatory level.