Background. Blood borne infections such as HIV, Hepatitis B (HBV), and Hepatitis C (HCV) are of great importance to governments and their implementing partners, especially among people who use drugs (PWUD) and people who inject drugs (PWID). Prevalence and determinants of HIV, HBV, and HCV among PWUD and PWID in Ghana are not well established, the significance of this study. Method. This assessment was a cross-sectional study implemented via the respondent driven sampling approach. A team of community advisory boards that comprised former users, current users, and civil society organizations were constituted to help in the implementation of the study. The study was conducted in four regions in Ghana. The assessment was based on a representation of populations of PWID and PWUD from the four regions. Efforts were made by the team to ensure adequate representation of women where feasible. A quantitative questionnaire was developed and used to obtain information on the respondents’ sociodemographics, sexual behavior, substance use, and biological characteristics. The prevalence of HIV, HBV, and HCV among PWID and PWUD was determined using blood samples. First response and oral quick test for confirmation of HIV positivity were carried out, while SD bioline was used to test for the presence of HBV and HBC. Data were analyzed using the Bayesian generalized linear model via the binomial family of distributions under the logit link function with weak Cauchy and Normal distribution as prior. Results. A total of 323 PWUD and PWID participants were interviewed across four regions of Ghana. The overall median age of the respondents was 36 (28, 43) years. The prevalence of HIV, HBV, and HCV infection in the study was 2.5%, 4.6%, and 5.9%, respectively. The prevalence of HIV, HBV, and HCV among drug users was 2.5% (95% CI: 0.7%–4.2%), 4.1% (95% CI: 1.8%–6.2%), and 6.7% (95% CI: 3.9%–9.4%), respectively. Most drug injectors and users started using and injecting drugs at ages less than 20 years and between 20 and 29 years, respectively. Drug users who identified themselves as part of the general population were 66% less likely to be tested HIV positive (POR = 0.34, CrI: 0.12–0.81) compared to sex workers. Part time employment respondents had fivefold odds (POR = 5.50, CrI: 1.20–16.16) of being HBV positive as against full-time employment. Conclusion. Most of the injectors and users started drugs at an early age. Drug users and injectors are at higher risk of these infections because of associated risky sexual behaviors and risky injection practices. Harm reduction programs to help addicts who are willing to quit the practice are recommended.