Abstract: This research aims to investigate the efficacy of the psychological empowering instruction on nurses' occupational compatibility and vitality at Apadana Hospital of Ahvaz. The participants of the study were 50 nurses of Ahvaz Apadana Hospital. They were randomly selected in two experimental and control groups via a simple sampling method. First, a pre-test was given to each group through a job-compatibility and vitality questionnaire. After that, the experimental group was exposed to the independent variable (Psychological Empowering Instruction) for 10–week sessions 90 minutes each. However, the control group did not receive any instruction. This semi-empirical study was experimental pre-test/post- test with a control group, and the follow- up test was conducted with one month interval after the post test. To analyze the data, multi- variable variance analysis (MANOVA) was run at sa = 0.05 significance level. The obtained results revealed that the psychological empowering instruction promoted occupational compatibility and vitality of the experimental group of the nurses in comparison with the control group, i.e. (P= 0.0001). Moreover, the impact of the mentioned instruction regarding the follow-up test result was stable.