Background: Healthcare workers’ hand hygiene remains a key pillar because it prevents and controls healthcare associated infections. Healthcare Workers’ hand hygiene compliance is suboptimal. Aim: The study developed contextualised guidelines for Healthcare Workers’ hand hygiene and infection control in patient care. Methods: The Precede-Proceed model with Theory of Planned Behaviour guided the study. The study was conducted following the mixed methodology approach, observational survey, exploratory, descriptive and contextual in nature study with mixed thematic analyses in a research wheel process. Data were collected through direct participant observation of hand hygiene opportunities through observing (n=95 Healthcare Workers; n=570 practices). Self-administered questionnaires were used to collect data from Healthcare workers (n=189) regarding challenges they faced in achieving hand hygiene. Structured interviews were conducted with patients (n=574). Retrospective reviews of healthcare associated infections and their associated mortalities were carried out from mortality records. Data were analysed retrospectively. Partly the data were statistically and mixed thematically analysed. Guidelines were developed using intervention alignment throughout, mapping, matching, pooling, patching and validation corroborated with Precede-Proceed models’ best practices. The study was ethically reviewed and approved by University of South Africa and the Medical Research Council of Zimbabwe project numbers, 6067662 and MRCZ/B/208. Results: Hand hygiene non-compliances were mostly found in the following contexts, after touching patients’ surroundings, and before doing an aseptic procedure. A non-hand hygiene compliance of Healthcare workers 167(29.3%) and compliance 403(70.7%) in context was suboptimal with sad patients and challenges faced by Healthcare workers. Conclusion: Healthcare Workers had gaps in hand hygiene compliance and availability of required resources. Gaps were also noted in ongoing hand hygiene promotion educational strategies and guidelines to comply and prevent. Guidelines to enhance hand hygiene included, attend to hand hygiene strictly after touching patient surroundings, bed linen, lockers and curtains to prevent gastroenteritis; follow standard precautions against HCAIs from spreading to patients' environments; and comply with hand hygiene guidelines, policies and regulations for best practice with patients. The study contributes generalisable knowledge. / Health Studies / D. Litt et Phil. (Health Studies)