Respiratory viruses are common in causing acute respiratory illnesses with significant annual morbidity and mortality. Detection of these viruses is critical to guiding appropriate patient management and infection control. To date, many viral infections are under–reported or misdiagnosed due to the limitations of current techniques available for routine respiratory viruses testing. Thus, we aimed to characterize circulating human respiratory viruses causing acute respiratory disease and hospitalization using real–time multiplex PCR. Of the 129 samples tested for human respiratory viral infections, 96 (74.42%) samples were positive for at least one virus, whilst the remaining 33 (25.58%) samples were negative for all. Among the positives, 60 (62.5%) cases were infected with a single respiratory virus, compared with 36 (37.5 %) cases infected with multiple respiratory viruses. Throughout the study period, the most prevalent viruses detected in both single– or multiple–infections were human rhinovirus (HRV) with 42 (43.75%) positive cases followed by human metapneumo virus, respiratory syncytial virus B, and influenza A virus infections with 20 (20.83%), 17 (17.71%), and 14 (14.58%) positive cases each, respectively. In summary, 45.7% of all hospitalized cases were infected with a single respiratory virus, and HRV was characterized as the dominant virus causing acute respiratory illness in Riyadh. Continued monitoring of circulating respiratory viruses in the region is necessary to understand their epidemiology.