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This paper focuses on the methodology development and application of reliability-based design optimization to a vehicle exhaust system under noise, vibration and harshness constraints with uncertainties. Reliability-based design optimization provides a systematic way for considering uncertainties in product development process. As traditional reliability analysis itself is a design optimization problem that requires many function evaluations, it often requires tremendous computational resources and efficient optimization methodologies. Multiple functional response constraints and large number of design variables add further complexity to the problem. This paper investigates an integrated approach by taking advantages of variable screening, design of experiments, response surface model, and reliability-based design optimization for problems with functional responses. A typical vehicle exhaust system is used as an example to demonstrate the methodology.