This paper presents a general frequency domain framework for predicting multimode coupled buffeting response of long-span bridges to nonstationary winds. Within this framework, the wind speed field, aerodynamic forces, and bridge response are separated into deterministic time-varying mean and evolutionary random fluctuating components. Under the assumption of low variation rate of mean wind speed, the time-varying mean and self-excited and buffeting forces are modeled in static force coefficients, flutter derivatives, and admittance functions, determined in a wind tunnel under stationary wind, but with consideration of nonstationary wind characteristics in a quasi-steady manner. The time-varying mean bridge response is calculated through static analysis at each time instant. The random buffeting response is expressed in generalized modal displacements governed by the equations of a frequency-dependent linear time-variant (LTV) system. An equivalent frequency-independent LTV system is introduced, which permits calculation of response impulse functions directly from system modal properties at each frozen time. Formulations are presented for calculating time-varying RMS value and evolutionary spectrum of bridge response and its extreme value distribution. The traditional buffeting analysis framework for stationary wind excitations is the special case of this general framework. Based on this analysis framework, the buffeting responses of a long-span suspension bridge with a center span of approximately 2,000 m under various nonstationary winds are investigated, which shed insights on the general characteristics of nonstationary wind load effects on long-span bridges. The effectiveness and accuracy of the framework are also confirmed through time domain Monte Carlo simulations. (C) 2014 American Society of Civil Engineers.