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Background Tazobactam/piperacillin (TAZ/PIPC), widely used for treating various infections, is often discontinued due to hypokalaemia, although the preventive measures remain unclear. This study aimed to identify the incidence, clinical characteristics and associated risk factors for TAZ/PIPC-induced hypokalaemia.Methods Hospitalised patients receiving TAZ/PIPC therapy for >2 days were included. The primary endpoint was the incidence of hypokalaemia (serum potassium level ≤3 mEq/L) and identification of associated risk factors. Survival classification and regression tree (CART) analyses were used to estimate HR (95% CI) and cut-off values for continuous variables.Results Of the 224 patients treated with TAZ/PIPC during the study period, 168 were included. The median time (min–max) to the incidence of hypokalaemia was 3 (2–14) days. Hypokalaemia was observed in 30 patients. Survival CART analysis identified baseline serum potassium level (cut-off value of 3.7 mEq/L) and diarrhoea as risk factors.Conclusions Monitoring serum potassium levels is recommended after treatment initiation of TAZ/PIPC therapy for patients with baseline serum potassium levels ≤3.7 mEq/L and diarrhoea.