Background <p>Patients continue to encounter barriers to communication in specialist outpatient healthcare. However, little is known about the factors associated with&#xa0;patient-physician communication barriers in specialist outpatient healthcare in sub-Saharan Africa. The purpose of this study was to examine the factors that predict communication barriers among patients who use specialist outpatient healthcare in Ghana.</p> Methods <p>Using a stratified random sampling technique, the study was designed as a cross-sectional survey involving 269 patients at the Komfo Anokye Teaching Hospital in Kumasi. Chi-square, Fisher exact test, and binary logistic regression were used to analyse the data.</p> Results <p>Approximately 12% of the participants experienced communication barriers in their utilisation of&#xa0;specialist outpatient healthcare. The results revealed that unmarried (AOR: 3.244; C1 1.228–8.567, p = 0.018), non-Christians (AOR: 3.934; CI 1.342–11.532, p = 0.013), those with perceived poor health status (AOR: 3.680; CI 1.590–8.517, p = 0.002) and patients who spent over 180&#xa0;min at the specialist outpatient department (AOR: 3.855; CI 1.659–8.962, p = 0.002) were significantly more likely to experience barriers to patient-physician communication.</p> Conclusions <p>These findings suggest the contribution of socio-demographic differences in barriers to patient-physician communication in specialist outpatient healthcare in Ghana. The study provides further evidence for barriers to effective communication between patients and subspecialty physicians in Ghana.</p>