Philosophiae Doctor - PhD / Literature on post-operative pain indicates that post-operative pain is inadequately managed in many countries including Ghana. Little was also known about post-operative pain (POP) response and management in Ghana. This study sought to describe post-operative pain response and management among Ghanaian surgical nurses and post-operative patients within the medico-socio-cultural context. It also explored factors that influenced POP response and management and subsequently aimed to develop clinical guidelines within which post-operative pain could be managed in the medico-socio-cultural context. Research questions answered included: „what are the factors influencing post-operative pain responses among surgical patients and nurses; what clinical guidelines would be appropriate to guide post-operative pain management within the medico-socio-cultural context of Ghana?‟The study was designed as a multi-step focused ethnography which allowed the exploration of a specific sub-culture such as the surgical environment. The philosophical underpinnings of ethnography permit the investigator to use different data collection methods to fully understand the phenomenon investigated. Data collection during the ethnographic exploration phase involved individual interviews, clinical observations, and review of patients‟ clinical charts. At the stage of guideline development, data was collected through participant/expert review, systematic literature review, and consensus forum. Participants were sampled purposively and included 53 interview participants, 27 expert reviewers, and 29 consensus panel members. Also, there were 16 sections of clinical observation and review of 44 charts. The participants included nurses, patients and their relatives, the multidisciplinary team, key informants, experts, and stakeholders. The study was conducted at the Korle-Bu Teaching Hospital (KBTH) and Ridge Hospital, in Accra, Ghana. Appropriate ethical clearance was sought and individual informed consent was obtained.Concurrent analysis of data was done applying the principles of thematic content analysis and data was managed with NVivo 9. Themes that emerged from the patients‟ data were subjectivism which described pain dimensions and expressions and factors that influenced patients‟ pain experience were psycho-socio-cultural factors such as personal inclinations and socio-cultural background; and health system factors such as personnel attitude and health financing.The study also found that nurses perceived POP as an individual phenomenon and responded to pain by administering analgesics and by employing non-pharmacologic measures such as positioning and reassurance. Factors that influenced the nurses‟ pain response were individual factors such as commitment, discretion, and fear of addiction; and organizational factors such as organizational laxity and challenges of teamwork. Patients‟ relatives were also influenced by empathy, faith, and commitment to care for their post-operative patients. The multidisciplinary team and key informants were influenced by knowledge and experience in their respective specialty areas. Subsequently, the clinical guideline developed had four dimensions which highlighted patient and family education,effective teamwork, effective leadership and monitoring, and use of contemporary evidence for POP management.The study recommended that health professionals should be conscious of the subjectivenature of pain and they should educate and involve the patient on pain management decisions. Also, hospital leadership and the multidisciplinary team should be actively involved in pain management.