Background <p>Non-medical use of tramadol has emerged as a significant public health concern in Ghana, particularly among young commercial drivers. Despite its growing prevalence, there is a lack of mixed-methods research exploring both the quantitative patterns and underlying motivations for the inappropriate use of tramadol. This study adopts a concurrent triangulation mixed-methods design to investigate the key factors driving tramadol use among young commercial drivers in the Tamale Metropolis.</p> Methods <p>A total of 434 participants were recruited through convenience sampling for the quantitative component, while 50 individuals who use tramadol participated in seven focus group discussions using snowball sampling. The study examined patterns of tramadol use, reasons for consumption, modes of intake, and sources of supply among young commercial drivers.</p> Results <p>The findings indicate that 60.1% of participants used tramadol for non-medical purposes, with 41.5% consuming it daily. The primary motivation for use was to enhance physical performance (39.2%), followed by pain relief (19.4%). Regarding the mode of consumption, 43.5% mixed tramadol powder with energy drinks, while 31.6% swallowed the tablets with water. On average, participants consumed 155&#xa0;mg of tramadol daily, often in unauthorized high-dose formulations. Alarmingly, 72.8% of users sourced tramadol from the black market.</p> Conclusion <p>The study highlights the widespread misuse of high-dose, non-prescribed tramadol among commercial drivers in the Tamale Metropolis. The illicit supply chain and unregulated distribution exacerbate the crisis. Addressing this issue requires stringent regulation of drug importation and distribution, alongside targeted awareness campaigns to educate young drivers about the risks associated with the inappropriate use of tramadol.</p> Clinical trial number <p>Not applicable</p>