Background: As health care struggles to meet increasing demands with limited resources, Lean has become a popular management approach. It has mainly been studied in relation to health care performance. The empirical evidence as to how Lean affects the psychosocial work environment has been contradictory. This study aims to study the interaction between Lean and the psychosocial work environment using a comprehensive model that takes Lean implementation information, as well as Lean theory and the particular context into consideration. Methods: The psychosocial work environment was measured twice with the Copenhagen Psychosocial Questionnaire (COPSOQ) employee survey during Lean implementations on May-June 2010 (T1) (n = 129) and November-December 2011 (T2) (n = 131) at three units (an Emergency Department (ED), Ward-I and Ward-II). Information based on qualitative data analysis of the Lean implementations and context from a previous paper was used to predict expected change patterns in the psychosocial work environment from T1 to T2 and subsequently compared with COPSOQ-data through linear regression analysis. Results: Between T1 and T2, qualitative information showed a well-organized and steady Lean implementation on Ward-I with active employee participation, a partial Lean implementation on Ward-II with employees not seeing a clear need for such an intervention, and deterioration in already implemented Lean activities at ED, due to the declining interest of top management. Quantitative data analysis showed a significant relation between the expected and actual results regarding changes in the psychosocial work environment. Ward-I showed major improvements especially related to job control and social support, ED showed a major decline with some exceptions while Ward-II also showed improvements similar to Ward-I. Conclusions: The results suggest that Lean may have a positive impact on the psychosocial work environment given that it is properly implemented. Also, the psychosocial work environment may even deteriorate if Lean work deteriorates after implementation. Employee managers and researchers should note the importance of employee involvement in the change process. Employee involvement may minimize the intervention's harmful effects on psychosocial work factors. We also found that a multi-method may be suitable for investigating relations between Lean and the psychosocial work environment.