[Background/Objectives] Mycoplasma hyopneumoniae (M. hyopneumoniae) is widespread in the global swine industry, leading to significant economic losses, and is particularly severe in native Chinese pig breeds. The Ningxiang pig, a well-known native breed in China, is susceptible to M. hyopneumoniae, exhibiting high morbidity and mortality rates. This study was designed to evaluate the clinical effectiveness of the M. hyopneumoniae live vaccine (strain 168). [Methods] The vaccine was delivered to 7-day-old piglets in the farrowing room through intrapulmonary administration, and its efficacy was compared with that of the M. hyopneumoniae inactivated vaccine (strain J). Four experimental groups were designed: Group 1 (inactivated vaccine + inactivated vaccine), Group 2 (live vaccine + inactivated vaccine), Group 3 (live vaccine), and Group 4 (control), which was not vaccinated. The production performance of each group was measured, and the lung lesion scores and pneumonia lesion reduction rates were evaluated at slaughter. Nasal swabs and serum samples were collected on days 0, 14, 28, 56, 84, 112, and 140 to assess SIgA, IgG antibody levels, and the M. hyopneumoniae pathogen. [Results] The results showed that Group 3 had the best production performance and clinical outcomes, with the lowest average lung lesion score, of 4.43 ± 2.44, which was significantly different from the other groups (*** p < 0.001). [Conclusions] This study provided scientific evidence to support vaccination strategies for preventing and controlling the M. hyopneumoniae in native pig populations.