Background: The literature that has investigated to what extent a change in employment contributes to good health is contradictory or shows inconsistent results. The aim of this study was to investigate whether an association exists between a change in employment and cardiovascular, musculoskeletal and neuropsychological diseases in a sample of 10,530 Belgian workers in a seven-year follow-up study period. Methods: The following factors were analysed: Demographic variables, a change in employment and the work-related risks. Individuals being on medication for cardiovascular, musculoskeletal, and neuropsychological diseases were used as proxies for the three health issues. Logistic regression models for autocorrelated data with repeated measures were used to examine each medication type. Results: A change in employment and psychosocial load can have an important effect on the health of cardiovascular employees. Demographic variables, such as BMI and age, are risk factors for all three medications. Repetitive, manual tasks, handling static, exposure to noise levels of 87 dB, mechanical and/or manual handling with loads, and shift work were found to be positively associated with medications taken for musculoskeletal diseases. Exposure to noise 80 dB(A), managing physical loads and night work were found to be associated with being on medication for neuropsychological diseases. Physical activity and skill levels were considered to be protective factors for being on medication for neuropsychological diseases. Conclusions: Change in employment and psychosocial load were found as two important risk factors for being on medication for cardiovascular (CVD). Dealing with loads, doing shift work and being daily exposed to the noise of 87 dB correlated with being on medication for musculoskeletal (MSD). Dealing with physical loads, doing night work and being exposed to the noise of 80 dB were risk factors for being on medication for neuropsychological (NPD). While doing physical activity and reporting higher skill levels were found to be protective factors for NPD.