BACKGROUND The purpose of this study was to assess the effects of seawater on nasal congestion and runny nose symptoms in adults with an acute upper respiratory infection (URI). MATERIAL AND METHODS This was a multicenter retrospective cohort trial of patients with acute URI and symptoms of nasal congestion and runny nose. The patients were assigned to 2 groups and were administered regular non-drug supportive treatment or supportive treatment with nasal irrigation with sea salt-derived physiological saline. The primary efficacy endpoint was the effective rate (percentage of patients with ≥30% symptom score reduction from baseline for nasal congestion and runny nose). RESULTS In total, 144 patients were enrolled, including 72 in each group, and 143 patients completed the study. Both groups had similar demographics and vital signs. The effective rates for nasal congestion and runny nose were significantly increased in the seawater group compared with patients in the control group (87.3% vs 59.7% for nasal congestion; 85.9% vs 61.1% for runny nose; both P<0.001). In addition, the 2 groups showed markedly different degrees of patient symptom score improvement in sleep quality and appetite (both P<0.01), but not in cough and fatigue (both P>0.05). There were no adverse events in either group. CONCLUSIONS The sea salt-derived physiological saline nasal spray device satisfactorily improved nasal congestion, runny nose, sleep quality, and appetite in adults with URI, with no adverse effects.