This study aims to investigate the implementation strategy, unintended consequences, and underlying barriers to mandatory antimicrobial stewardship (AMS) programs in China. Face-to-face, in-depth qualitative interviews were conducted in 16 public hospitals in eastern, central, and western China. Hospitals were purposely selected with full consideration to represent both economically developing and developed areas and both secondary and tertiary care hospitals. A total of 111 respondents were interviewed, including 38 doctors, 28 clinical pharmacists, 15 microbiologists, 14 infection prevention and control specialists, 10 experts from medical service departments, and 6 quality improvement experts. A thematic framework analysis was conducted. A common implementation strategy was found among the surveyed hospitals in response to the AMS programs mandated by healthcare authorities. The hospital leadership empowered an AMS team to set AMS-related indicators for each clinical department and each doctor, and adopted core elements of AMS to optimize antimicrobial prescribing. However, the mandatory AMS approach also caused unintended consequences including regulatory circumvention, shift of risk to doctors and patients, and demotivation of healthcare workers. Two key barriers to AMS implementation were identified: (i) poor communication and cooperation between the AMS team and doctors, characterized by a high-power-low-power dynamic within hospital disciplines; and (ii) the profit-driven compensation system, which discourages collaboration and resource distribution for AMS implementation. Mandatory AMS programs should intensify AMS training, promote communication and cooperation between the AMS team and doctors, adjust the compensation system to facilitate better AMS implementation, and offer supportive measures that enable the adoption of strict regulations.