A growing interest in human resource management (HRM) in small and medium enterprises (SMEs) has not been accompanied by increased knowledge of how different HRM policy orientations can affect SMEs' effectiveness. In this way, the goal of this paper is twofold: to test whether the orientation of HRM towards high-performance work practices (HPWP)represented by the Abilities-Motivation-Opportunities (AMO) framework-allows SMEs to achieve better performance and to test the moderating role of corporate social responsibility (CSR) orientation. Based on a telephone questionnaire together with data collected from a sample consisting of 1,136 Spanish SMEs that operate in the industrial or services sector, our results show that SMEs perform better when HRM policies are oriented towards the AMO model. In addition, our findings highlight that this performance impact of orienting HRM towards HPWP is positively moderated by a CSR orientation. This paper thus complements HRM-related literature by adding new evidence exploring the impact of the AMO model on firm performance as well as the role played by CSR orientation within the SME context. Implications for the central European audience: Managers should be aware of the importance of considering and implementing appropriate ability, motivation, and opportunity policies for their employees in order to enhance SME performance. In addition, the importance of a CSR orientation is highlighted, which intensifies the impact of HPWP on firm performance. This empirical paper brings evidence from the underexplored high-performance work policies in SMEs, given their importance in stimulating employee and organizational performance. It also takes into account the particularities of the Spanish context, where most businesses are considered to be SMEs.