Background: In modern business conditions, intangible assets have a dominant impact on the business performance of the company. R&D activities, the level of R&D investments and the efficiency of R&D investments affect company profitability. There are various performance indicators of R&D activities that have an impact on profitability. Purpose: Bearing in mind that R&D is the precondition of growth and development of the company, as well as the efficiency of R&D investments, is the key determinant of economic corporate responsibility, the purpose of this paper is to investigate the effects of various performance indicators of R&D activities on companies' profitability. The aim of this paper is to investigate the effects of R&D investments, R&D intensity and return on R&D capital on the profitability of highly innovative companies. Study design/methodology/approach: Correlation, regression and cluster analyses were performed to provide an empirical investigation of the impact of key R&D performance indicators on the return on assets (ROA) of highly innovative companies, which are on the list of the top R&D spenders in the world. The data for the analysis comprises 24 R&D-intensive companies for the period 2013-2021. Findings/conclusions: The regression analysis results conducted on the determined clusters show that all three analyzed indicators of R&D activities have a positive and statistically significant impact on ROA in highly R&D-intensive companies. It is confirmed that the effects of various indicators of R&D activities are bigger in companies with higher RDII. Limitations/future research: The sample encompasses the 24 companies listed among the top 50 R&D spenders worldwide, which is considered insufficient for extensive analysis. The other limitation is related to the short research period. As the R&D activities produce yields after several years, the possible direction for future research is to investigate the impact of accumulated R&D investment over several years on ROA.