The burden of chronic kidney disease in Africa is three to four times higher compared to high-income countries and the cost of treatment is beyond the reach of most affected persons. The best treatment for end stage renal disease is kidney transplantation which is not available in most African countries. As kidney transplantation surgery is emerging in Ghana, this study assessed factors which could influence the willingness of patients with chronic kidney disease to accept it as a mode of treatment. This cross-sectional survey was carried out among patients with chronic kidney disease in Korle-Bu Teaching Hospital. A consecutive sampling method was used to recruit consenting patients. A structured questionnaire and standardized research instruments were used to obtain information on demographic, socio-economic characteristics, knowledge about transplantation, perception of transplantation, religiosity and spirituality. Logistic regression model was used to assess the determinants of willingness to accept a kidney transplant. 342 CKD patients participated in the study of which 56.7% (n = 194) were male. The mean age of the participants was 50.24 ± 17.08 years. The proportion of participants who were willing to accept a kidney transplant was 67.3% (95%CI: 62.0-72.2%). The factors which influenced participants' willingness to accept this treatment included; willingness to attend a class on kidney transplantation (p < 0.016), willingness to donate a kidney if they had the chance (p < 0.005), perception that a living person could donate a kidney (p < 0.001) and perceived improvement in quality of life after transplantation (p < 0.005). The barriers for accepting kidney transplantation were anticipated complications of transplant surgery and financial constraints. More than two-thirds of CKD patients were willing to accept a kidney transplant and this is influenced by multiple factors. Government health agencies must consider full or partial coverage of kidney transplantation through the existing national health insurance scheme. Further, efficient educational programmes are required to improve both patients' and physicians' knowledge on the importance of kidney transplantation in the management of end stage renal disease in Ghana.