Vibration and noise reduction methods are important research directions in many industries. Mufflers are widely used in pipelines to reduce noise and vibration transmission. A theoretical analysis is conducted to determine the noise reduction mechanism of a muffler with a side outlet, and the results are verified with experiments. The quadrupole parameters of the muffler are obtained using transfer matrix analysis, and sensitivity analysis of the quadrupole parameters is conducted. The influence of the side outlet location on the transmission loss of the muffler is investigated experimentally using an impedance tube. The key factors affecting the transmission loss are analyzed. The theoretical calculation results of the transmission loss of the side outlet muffler are in good agreement with the experimental results.