New psychoactive substances (NPS) have emerged as a growing threat in Taiwan, yet their clinical severity compared with traditional illicit drugs (TID) remains uncertain. This study aimed to compare the clinical characteristics and critical outcomes between patients with NPS and TID poisoning confirmed by liquid chromatography–tandem mass spectrometry (LC–MS/MS).

We conducted a multicenter retrospective cohort study across 10 hospitals within six medical systems in Taiwan. Between March 2019 and January 2020, 1,378 patients with suspected drug intoxication underwent urine LC–MS/MS analysis at certified toxicology laboratories. A total of 362 patients (26.3%) tested positive, including 147 (40.6%) with NPSs, 130 (35.9%) with TIDs, and 85 (23.5%) with mixed substances.

Demographic, clinical, and laboratory data were collected through a chart review. Synthetic cathinones and ketamine analogs were the most frequently detected NPSs, whereas methamphetamine/amphetamine and morphine were predominant among TID cases. Critical outcomes were defined as intensive care unit admission or death in the emergency department. The overall rate of critical outcomes was 18.3% (252/1,378). The odds of critical illness did not significantly differ between NPS and TID users (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.51–1.74). Kaplan–Meier survival analysis revealed no significant difference in short-term survival among the NPS, TID, and mixed-drug groups (log-rank p = 0.665).

No statistically significant difference in clinical severity or mortality risk was observed between NPS and TID poisoning. These findings highlight that NPS exposure has a similar potential for critical illness and should be managed with the same clinical vigilance as conventional drug poisoning.