Aims: Medication error is a persistent and far-reaching clinical problem. Unsafe medication practices often occur due to unresolved medication errors, poor compliance with rules and policies, and the low clinical applicability of such rules and policies. This study, conducted in a Hong Kong hospital, aimed at addressing these concerns and developing a new model for drug administration and enhancing safe clinical practice based on research evidence. The current drug administrative procedure of \u27three checks\u27 and \u27five rights\u27 was reviewed to examine adherence and applicability in clinical settings. Methods: The study adopted a mixed method, with both quantitative and qualitative research designs. Data collection involved a review of medication incidents involving nurses that occurred over a 1-year period at the hospital, focus group interviews of nurses (n = 29), questionnaires for nurses (n = 466) and nurse managers (n = 12), observational studies of nurses (n = 46; 210 observations), and individual interviews (n = 3). Results: The common causes of medication errors were non-compliance with policies or procedures, doctor\u27s illegible writing, wrong transcription of drug administration times, failure to check for the right patient, wrong identification of drugs, and distractions. Many nurses regarded the \u27golden rule\u27 of \u27three checks\u27 and \u27five rights\u27 for drug administration as impractical and not viable because of time constraints, manpower shortage, and heavy workloads. Research data from questionnaires and observation studies validated the appropriateness of \u27five rights\u27 in preventing medication errors, but also supported a reduction of the \u27three checks\u27 practice to \u27two checks\u27. Conclusion: A new model of drug administration that is more practical, applicable, and safe in clinical practice is proposed. It is suggested that this model, which adopts \u27two checks\u27 and \u27five rights\u27 for drug administration, be tested further as a model that can save nurses\u27 time, enhance effective checking, and reduce medication error incidents