Over the past two decades, there has been an explosion in the volume of research examining the impact of HR on company performance. A central theme of this research has been how High Performance Work Systems (HPWS) impact on the competitiveness and innovative capabilities of firms. The literature reveals a theoretical divergence between the ‘universalistic’ perspective and others including the ‘contingency’ approach. This study undertook to examine these issues by looking at the impact of HPWS on innovation performance in a multi-industry sample of firms in Ireland. A survey was conducted on a sample of 1000 larger firms, yielding complete responses from 132 firms. Data from respondent firms was based on responses from both the general manager and the human resource manager. The impact of HPWS on three measures of innovation performance (workforce innovation, innovation revenues and innovation competitiveness) was examined, and HPWS was found to have a significant impact on innovation performance when controlling for a range of variables. The moderating roles of R&D strategy, dynamic environment and organisational culture on HPWS were assessed. No moderating effect was found for workforce innovation or innovation revenues, but a clear moderating effect was found for innovation competitiveness. Finally, a series of significant differences were found in relation to innovation performance and HPWS levels between Irish-owned firms and US and European firms. Implications arising from the findings for researchers, practitioners and policy-makers are considered.