The provision of quality and affordable healthcare remains a challenge for many countries and has been shown to be constrained by many factors including economic, social and political factors. This then results in an imbalance between the supply and demand for health services. Shortage of skilled health workers then provides further strain on improving access to quality health services. Therefore, there is a need to establish how to make the most of this rare resource, including how to work on the retention of the health care workers. The study was anchored on Herzberg Two Factor Theory that argues that individuals are interested at two different areas of motivation. First level includes psychological needs such as advancement, personal growth, the nature of work, responsibility, and achievement (motivators). Second group of factors the “hygiene/extrinsic are work related like salaries, work conditions, policies and administration. This study aim was to investigate the effect of staff’ motivation on the retention of nurses at Kenyatta National Hospital (KNH). The specific objectives were to determine the effect of financial incentives, career development, working conditions and personal factors affecting retention of nurses in Kenyatta National Hospital- Kenya. Using a mixed methods cross sectional study design, both quantitative and qualitative data was collected from nurses working at Kenyatta National Hospital (KNH). A sample of 228 nurses were randomly selected for self-administered questionnaires for the study. To complement the quantitative data, qualitative data was collected through purposive in-depth interviews with 10 departmental heads in the nursing cadre to understand factors that influenced nurse’s motivation at work. The quantitative data was analyzed using Statistical Package for Social Scientist (SPSS). Descriptive statistics such as frequencies and percentages were used to summarize data while logistic regression was used to estimate adjusted odds ratios. Qualitative data was analysed manually using thematic analysis of issues emerging from the data and informed by findings from the questionnaires. Results showed that nurse’s intention to leave KNH was 60 percent and that age, education, availability of career development initiatives, desire for better working conditions and need for a better pay significantly influenced nurses’ intention to leave KNH. The recommendations from this study include ensuring revision of any CBA agreed on that will look into nurses being paid for overtime hours worked, access car loans and mortgages, ensure nurses are provided with basic career development opportunities such as career talks and scholarship opportunities. Additionally, nurses ought to be provided with good social welfare facilities. The other incentive is provision of clean and safe work environment for nurses. And importantly to review workload at the facility to allow fair distribution and motivate their nurses