Traditional medicine (TRM) use remains universal among individuals, families and communities the world over but the predictive variables of TRM use is still confounding. This population-based study analysed the predictors of TRM use in Ashanti Region, Ghana. A retrospective cross-sectional quantitative survey involving systematic random sampled participants (N = 324) was conducted. Structured interviewer-administered questionnaires were used as research instruments. Data were analysed with logit regression, Pearson's Chi square and Fisher's exact tests from the PASW for Windows application (V. 17.0). Overall, 86.1 % (n = 279) reported use of TRM with biologically-based and distant/prayer therapies as the major forms of TRM utilised in the previous 12 months. Among the general population, TRM use was predicted by having low-income levels [odds ratio (OR) 2.883, confidence interval (CI) 1.142-7.277], being a trader (OR 2.321, CI 1.037-5.194), perceiving TRM as effective (OR 4.430, CI 1.645-11.934) and safe (OR 2.730, CI 0.986-4.321), good affective behaviour of traditional medical practitioner (TMP) (OR 2.943, CI 0.875-9.896) and having chronic ill-health (OR 3.821, CI 1.213-11.311). The prevalence of TRM use is high. The study provides evidence that people's experience, personal attributes, health beliefs, attitude to TRM, attitude of TMP to clients and medical history are largely accountable for the upsurge use of TRM rather than socio-demographic factors. Understanding the health-seeking behaviour of individuals is exigent to ascribe appropriate medical care by health care providers.