Antibiotic self-medication in patients with respiratory tract infections (RTI) is increasing globally and has been reported to be one of the prime contributors to antimicrobial resistance (AMR). Our study aims to provide data on the prevalence of antibiotic self-medication and identify the factors contributing to self-medication in adult patients with respiratory tract infection in an urban setting in Cameroon. This was cross-sectional study carried out at Mboppi Baptist Hospital, Douala, Cameroon. A validated structured questionnaire was administered to 308 consenting participants with diagnosed RTIs, to collect data on socio-demographic characteristics and history of antibiotic self-medication. Significance was set at a p-value < 0.05. The prevalence of antibiotic self-medication amongst individuals with RTIs was 41.9% (95% CI 36.5% to 47.5%). Patients with a history of pulmonary tuberculosis (TB) were significantly less likely to self-medicate with antibiotics (p-value = 0.043). The most common source of antibiotic self-medication was pharmacies (62%) and Cotrimoxazole and Amoxicillin were the most commonly used antibiotics (38.8% (50), 26.4% (34), respectively). Self-medication with antibiotics in adult patients with RTIs is common in Cameroon. Control of the use of antibiotics, organisation of medication stewardship programs, and education of the general population on the adverse consequences of antibiotic self-medication are required.