Loosening of bolted connections in a structure can significantly reduce its load-bearing capacity. Detecting loosening of bolted connections at an early stage can prevent failure of the structure. Due to the complex geometry of a bolted connection and material discontinuity between clamped components, it is difficult to detect loosening of a bolted connection using conventional nondestructive test methods. A vibration-based method that uses changes in natural frequencies of a structure to detect locations and extent of damage can be used to detect loosening of bolted connections since the method focuses on detecting a stiffness reduction, which can result from loosening of bolted connections. Experimental and numerical damage detection was conducted to detect loosening of bolted connections in a full-size steel pipeline with bolted flanges using the vibration-based method. With the recent development of a modeling technique for bolted connections in thin-walled structures, an accurate physics-based finite element model of the pipeline that is required by the vibration-based damage detection method is developed. A trust-region search strategy is employed to improve the damage detection method so that global convergence of the damage detection algorithm can be ensured for underdetermined systems, and robustness of the algorithm can be enhanced when relatively large modeling error and measurement noise are present. The location and extent of loosened bolted connections were successfully detected in experimental damage detection using changes in natural frequencies of the first several elastic modes of the pipeline; the exact location and extent of the loosened bolted connections can be detected in numerical simulation where there are no modeling error and measurement noise.