This paper presents the results of an empirical study of training procedures enabling flexibility in the design and management of large-scale engineering systems. The work relies on the development and use of a simulation game environment to study decision-making dynamics under different treatment conditions. Evaluation of short-term, long-term, and in-game training is completed to assess the main and interaction effects on quantitative lifecycle performance indicators, and qualitative user impressions. Forty-six graduate engineering students participated in controlled experiments where they worked on the design and management of a flexible emergency medical services system. Results show that in-game training produces a statistically significant improvement on lifecycle performance score, while long-term flexibility training significantly reduces decision-making time. In-game training improves process satisfaction. Both short-term and in-game training lead to improved satisfaction with the results, and contribute to improved anticipated quality of the results. Correlation studies suggest that participants taking more time for decision-making may improve lifecycle performance scores. Lifecycle score improvement also increases as satisfaction with the process and anticipated quality of results increase. Experimental results show that different training procedures produce different effects on design and management decision-making for flexible engineering systems operating under uncertainty. They provide further insights to support the development and evaluation of novel training approaches useful for systems engineering practice and education.