Background: Analgesic poisoning is common in Hong Kong. Analgesics containing salicylate are easily available. Salicylate poisoning may be encountered in the daily practice of the accident and emergency department. The issue of routine salicylate screening was discussed in a number of articles, and the viewpoints of most authors were that routine salicylate screening was unnecessary. Objectives: The primary outcome is to explore the predictive factors of supratherapeutic peak serum salicylate level (>2.17 mmol/L) and delineate the role of routine screening serum salicylate level in poisoned patients attending the accident and emergency department. Methods: This is a retrospective cohort study. Poisoning cases presented to Hong Kong Poison Information Centre between 1 July 2008 and 31 October 2020 with serum salicylate level checked were included. The demographics, laboratory parameters and clinical outcomes were reviewed. Results: There were 8673 cases included with serum salicylate level checked, accounting for 17% of all poisoning cases. Sixty-six (0.76%) cases had supratherapeutic peak serum salicylate level and 11 (0.13%) of them were undeclared salicylate ingestion. Worse clinical outcomes were observed in cases with supratherapeutic peak serum salicylate level. Univariate analysis showed that tinnitus, hyperthermia, alkalaemia, metabolic acidosis, respiratory alkalosis and therapeutic use of aspirin were significantly associated with supratherapeutic peak serum salicylate level. Variables with p < 0.3 were entered into the backward stepwise logistic regression by likelihood ratio. A clinical prediction rule with three attributes (tinnitus, therapeutic use of aspirin and partial pressure of CO2 <5 kPa) was derived. It showed 100% sensitivity in internal validation. Conclusion: Serum salicylate level should be checked in poisoned patients with (1) tinnitus, (2) the therapeutic use of aspirin or (3) partial pressure of CO2 <5 kPa in arterial or venous blood gas. Routine salicylate screening remained a tool for clinicians not experienced in toxicology.