A 67-year-old woman with a 16-year history of hemodialysis because of diabetic kidney disease received maintenance dialysis therapy for 3.5 hours 3 times a week. Weight gain was approximately 4% of her basic weight (40.2 kg). Blood pressure was 190/90 mmHg on awakening, 120/60 mmHg in a sitting position before dialysis, and rose to 200/90 mmHg in a supine position soon after the start of dialysis. It decreased to 90/50 mmHg upon standing after dialysis, and thereafter the patient could hardly stand up for the rest of the day. The application of transdermal nitroglycerin (Nitroderm TTS^®) at the start of dialysis was effective for preventing the increase in supine blood pressure during dialysis, with the blood pressure maintained at 150/80 mmHg. Long-term administration of oral amezinium metilsulfate (Risumic^® 10 mg) was ineffective for preventing orthostatic decrease in blood pressure. Only slight improvement was observed with the administration of oral droxidopa (DOPS^® 100 mg) before and after the end of dialysis. The additional administration of an oral acetylcholinesterase inhibitor, distigmine (Ubretid^®), before the end of dialysis significantly reduced the incidence of general malaise and gait disturbance. Symptoms were markedly improved to the extent that the patient could perform daily life activities, including shopping and household chores. The coexistence of supine hypertension and orthostatic hypotension is not rare in diabetic hemodialysis patients. The application of transdermal nitroglycerin at the start of dialysis prevented the increase in supine blood pressure during dialysis. The use of acetylcholinesterase inhibitors to treat orthostatic decrease in blood pressure at the end of dialysis led to an improvement in the patient's QOL.