Introduction: Diabetes mellitus is a common cause of kidney failure and is often complicated by autonomic neuropathy, which may have implications for blood pressure (BP) homeostasis during hemodialysis (HD). Methods: In this post hoc analysis of the Frequent Hemodialysis Network (FHN) Daily Trial, we used random effects Poisson and linear regression models to estimate the association of diabetes (vs. not) with intra-dialytic hypotension (IDH) and peri-dialytic BP parameters, respectively. We tested for differential associations according to the randomized treatment (6/week vs. 3/week HD) and pre-HD systolic BP. Results: Of the 244 patients with intra-dialytic BP data, 100 (41%) had diabetes at baseline. The mean age was 51 ± 14 years; overall, 39% were female. In adjusted models, diabetes (vs. not) was associated with a 93% higher risk of developing IDH (IRR: 1.93; 95% CI: 1.26, 2.95). There was no evidence that the randomized treatment assignment modified the association between diabetes and IDH (pinteraction = 0.32), but more potent associations were noted among those with higher pre-HD systolic BP (pinteraction < 0.001). Diabetes (vs. not) was associated with a lower adjusted nadir intra-HD BP (-4.2; 95% CI: -8.3, -0.2 mm Hg) but not with the pre- or post-HD systolic BP. Conclusions: Among participants of the FHN Daily Trial, patients with diabetes had a higher risk of IDH and lower nadir intra-HD systolic BP than patients without diabetes, even when undergoing HD up to 6 times per week.