BACKGROUND: Acute respiratory infections (ARI) are associated with a huge morbidity and mortality worldwide. Rhinoviruses (RVs) and Enteroviruses (EVs) are recognized as leading causes of ARI. OBJECTIVES: The present study describes the molecular epidemiology of RVs and EVs in Cameroon over a 3-year surveillance period. METHODS: From September 2011 to October 2014, nasopharyngeal swabs were collected from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARI). Two sub-genomic regions of the EVs and RVs were targeted for molecular characterization. These included the most conserved 5\'-untranslated region (5\'UTR) and the viral protein 4/viral protein 2 transition region (VP4/VP2). RESULTS: A total of 974 samples were collected. Children </=5 years accounted for 85.7% (835/974) of all participants. Among them, 160 (16.4%) were positive for RVs and/or EVs. RVs and/or EVs were significantly more identified in ILI compared to SARI patients (P = .015). Both viruses co-circulated all year long with a marked increase of occurrence during rainy and cold season. All RV species were found to circulate in Cameroon, with 6, 10 and 6 virus types belonging to the RV-A, RV-B and RV-C, respectively. EV species identified comprised EV-A (1 Coxsackie virus A5), EV-B (1 Coxsackie virus A9 and 2 Coxsackie virus B1) and EV-C (1 EV-C117). CONCLUSIONS: This study indicates a strong year-round occurrence of EV and RV associated respiratory infections in Cameroon. Molecular characterization identified a wide variety of RVs and EVs in patients with ARI in Cameroon.