A series of variants of antithrombogenic poly­(2-methoxyethyl acrylate) with controlled side-chain spacing were prepared via regio-selective ring-opening metathesis polymerization. In general, understanding the hydration state and its dynamics at the polymer/water interface is important for the development of biomaterials. To determine how the chemical design of polymeric materials can control the hydration state, we systematically investigated the effect of side-chain spacing not only on the hydration state but also on thrombogenicity. The hydration state of novel polymers was determined by evaluating the thermodynamic behavior at low temperatures using differential scanning calorimetry measurements. Under physiological ionic conditions in phosphate-buffered saline [PBS(−)], the amount of intermediate water (IWPBS), which is the fraction of hydration water showing cold crystallization near the homogeneous nucleation temperature, decreased monotonically with increasing side-chain spacing. Thrombogenic properties were evaluated by the human platelet adhesion test, quartz crystal microbalance measurements, and enzyme-linked immunosorbent assays. All thrombogenic reactions were activated with the expansion of the side-chain spacing except for albumin adsorption. The present study revealed a clear correlation of IWPBS with antithrombogenicity and the possibility of controlling IWPBS by simply changing the side-chain spacing of the polymers.