This paper adopts an integrative and complementary approach to the universalistic and contingency frameworks for analyzing the effectiveness of high-involvement work practices (HIWPs) in Spanish manufacturers. It focuses on some practices that firms adopt at operational level (decentralization, teamwork, job enlargement, information and knowledge sharing and performance-based compensation) to enhance operational performance (cost, quality, flexibility and delivery) and financial performance (return on asset), dealing with the possible moderating effect of three contextual variables: firm age, firm size and trade union power. Using moderated hierarchical regressions and data from 265 Spanish manufacturers, our results show that three of the five HIWPs considered in our study have direct effects on business performance. We also find that three contextual variables have moderating effects on the relation between HIWPs and business performance. Our paper contributes to the debate over the respective merits of the universalistic and contingency frameworks; it offers a broader view about the type of contemporary human resources practices that are successful in the Spanish industrial sector, and in a European manufacturing context, and may guide managers when assigning their firms’ limited resources to the most relevant human resources practices in each particular setting, considering internal characteristics, such as firm age, firm size and trade union power.