BackgroundThere are progressively alarming rates of non-medical use, addiction and possible dependence on tramadol in low-middle-income countries. Tramadol is known to heighten negative consequences on social interactions, physical and cognitive abilities among adolescents, students and youth, particularly those with polysubstance use. However, literature on the use of tramadol in low-middle-income countries, especially among undergraduate university students in Ghana remains inadequate. Thus, this study sought to determine the prevalence and factors associated with tramadol use among undergraduate students in Ghana. MethodsAn institutional-based cross-sectional study and a quota sampling technique were employed to gather data from January to March 2023 on 600 undergraduate students from the University for Development Studies, Tamale, Ghana and analyzed with SPSS (version 26.0). Multiple logistic regression model was used to identify factors associated with the use of tramadol (p-value <= 0.05). ResultsThe lifetime prevalence of tramadol use was 17.8%. Among those who used tramadol in their lifetime, 14.95% used tramadol alone whereas 85.05% used at least one substance alongside tramadol. The study recorded more females (67.8%) than males. Students aged 20-24 years (20.5%), those single/never married (18.7%), those renting/living alone (19.7%) and first year students (17.4%) accounted for the majority of groups at high risk of lifetime tramadol use. To improve academic performance was the primary reason for initiating tramadol use. Male sex (adjusted odds ratio [AOR] 2.673; 95% confidence interval [CI] 1.590-4.493; p < 0.0001) and those with lifetime cannabis use (AOR 2.137; 95%CI 1.267-3.604; p = 0.004) were significantly associated with lifetime tramadol use. ConclusionsThis study revealed that lifetime tramadol use was high. Male sex and those with lifetime cannabis use were significantly related with lifetime tramadol use. The use of tramadol has become a public health threat and is important to limit its incidence and continuous use through extensive school and community health campaigns and strengthening of governmental policies against tramadol and other substance use since they increase the propensity of unwarranted cognitive, physical and social outcomes.