BACKGROUND Anesthetic care for termination of atrial fibrillation with catheter ablation poses significant challenges due to significant pain lengthy procedure. A delicate polypharmacy combining anaesthetic agents to minimize respiratory depression and hemodynamic changes and to provide satisfactory sedation and analgesia is needed. METHODS Ninety-eight patients were randomized into two groups receiving either two gram of propacetamol or normal saline intravenously for 20 min before anesthesia. Monitored anesthesia care was provided with midazolam and remifentanil. RESULTS Total amounts of remifentanil infused were similar between the groups (626±251 μg vs. 597±315 μg, P = 0.606). Accounting for the mean duration of the procedure and the elimination half-life of propacetamol, remifentanil requirements were significantly less among patients whose procedure ended within 180 min (n = 56) in the Propacetamol group than those in the Control group (540±194 μg vs. 421±164 μg, P = 0.017). In the Control group, the incidence of analgesics usage 24 h after the procedure was significantly greater (43% vs. 23%, P = 0.038), and patients exhibited a higher pain score (3.1±2.1 vs. 1.9±2.1, P = 0.007), compared to the Propacetamol group. CONCLUSIONS The addition of a single dose of pre-emptive propacetamol showed promising results in terms of opioid consumption in patients whose procedure ended within 180 min. It provided better post-procedural pain control, compared with midazolam plus remifentanil alone.