As an emerging building solution, cross-laminated timber (CLT) floors have been increasingly used in mass timber construction. The current vibration design of CLT floors is conservative due to the assumption of simple support conditions in the floor-to-wall connections. It is noted that end fixity occurs as a result of clamping action at the ends, arising from the gravity load applied by the structure above the floor and by the mechanical fasteners. In this paper, the semi-rigid floor-to-wall connections are treated as elastically restrained edges against rotations to account for the effect of partial constraint. A rotational end-fixity factor was first defined to reflect the relative bending stiffness between CLT floors and elastic restraints at the edges. Then, for the design of vibration serviceability of CLT floors as per the Canadian Standard for Engineering Design in Wood (CSA O86), restraint coefficients were defined and their analytical expressions were derived for natural frequencies and the mid-span deflection under a concentrated load, respectively. In particular, a simplified formula of the restraint coefficient for the fundamental frequency was developed to assist engineers in practical design. At last, by comparing with reported experimental data, the proposed design formula showed excellent agreement with test results. In the end, the proposed end fixity factor with their corresponding restraint coefficients is recommended as an effective mechanics-based approach to account for the effect of end support conditions of CLT floors.