Schizophrenia is a chronic condition associated with poor psycho-social and medical outcomes. Non-adherence to antipsychotic medications accounts for most of the relapses in schizophrenia, resulting in frequent hospital readmissions, self-harm, violence, and poor cognitive, clinical, and functional outcome. This multi-center study examined the role of therapeutic alliance in medication adherence. One hundred and eight (108) schizophrenia patients aged 18-60 years were recruited for the study through a purposive sampling technique. The study was conducted at the Bono Regional Hospital and the Sunyani Municipal Hospital in Ghana. The Medication Adherence Rating Scale (MARS) and the Scale to Assess the Therapeutic Relationship-Patients version (STAR-P) were adapted for the study. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 25. Most of the respondents were between 18 and 35 years (85.2%) of age. Males constituted 61.1% of the sample. A larger proportion of the respondents were residents of urban communities (66.7%). More than half of the sample did not have any formal education (51.9%) and 51.9% were unemployed. The mean (standard deviation) for the overall medication adherence and the therapeutic alliance was 4.56 (± 1.715) and 42.16 (± 7.710) respectively. There was no association between overall therapeutic alliance and medication adherence, rs = .14, n = 108, p = .146. However, affective bond showed a weak negative correlation with medication adherence, rs = .19, n = 108, p = .044. This finding indicates the need for clinicians to consistently seek patients’ views and concerns at each level of their treatment to achieve optimum outcomes.