Background/Aim: Pulse pressure (PP) is a result of arterial stiffness seen in dialysis patients, but may be a consequence of fluid overload. We examined the role of β<sub>2</sub>-microglobulin (β<sub>2</sub>M) in PP in relation to metabolic alterations in patients on different hemodialysis (HD) modalities. Methods: We studied 76 hemodialyzed patients on regular HD (n = 34), predilution bagged hemodiafiltration (n = 19) and online predilution hemodiafiltration (n = 23). β<sub>2</sub>M levels were measured by radioimmunoassay, and the clearance of β<sub>2</sub>M was assessed by Kt/V for β<sub>2</sub>M. Arterial stiffness was measured as carotid-femoral pulse wave velocity, and PP was derived. Insulin levels were measured using immunoradioassay, and insulin resistance was calculated using homeostasis model assessment insulin resistance (HOMA-IR). Serum bicarbonate levels were measured using a blood gas analyzer, and percent sodium removal was calculated. Results: β<sub>2</sub>M levels predict increased PP (p = 0.02) adjusting for age, HD modalities, HD duration, HOMA-IR and percent sodium removal. β<sub>2</sub>M was positively associated with HOMA-IR (r = 0.306, p = 0.007). Serum bicarbonate levels and carotid-femoral pulse wave velocity were inversely associated (r = –0.719, p = 0.001). Conclusions: β<sub>2</sub>M levels were positively associated with PP, which was influenced mainly by dialysis modality fluid and sodium balance and less by arterial stiffness. β<sub>2</sub>M levels were positively associated with insulin resistance. Uremic acidosis may contribute to arterial stiffness.