Background: Unlike atrial fibrillation (AF), atrial flutter (AFl) is thought to be relatively refractory to pharmacological cardioversion (PC), but the evidence is scarce. The aim of this study was to evaluate the clinical characteristics and efficacy of the PC of AFl with amiodarone in comparison to AF. Materials and methods: This retrospective study covered 727 patients with urgent consult for AF/AFl in a high-volume emergency department between 2015 and 2018. AFl was diagnosed in 222 (30.5%; median age: 68 (62; 75) years; 65.3% men). In a nested case-control study, 59 control patients with AF, matched in terms of age and sex with 60 AFl patients, were subject to PC with amiodarone. The primary endpoint was return of sinus rhythm confirmed using a 12-lead ECG. Results: The AFl population had a median CHA2DS2-VASc score of 3 (2; 4) and episode duration of 72 h (16; 120). In the AFl cohort, 36% of patients were initially subject to PC, 33.3% to electrical cardioversion (EC) and 40.5% to catheter ablation. In comparison to the AF group, the AFl patients required a longer hospitalization time, had a higher rate of EC (p< 0.001) and less frequent use of PC (p< 0.001) and, lower left ventricular ejection fraction (p< 0.001) and more pronounced cardiovascular risk factors. The efficacy of PC with amiodarone was significantly lower in AFl than AF group (39% vs. 65%, relative risk (RR) 0.60,p= 0.007). Conclusions: AFl patients shared a greater burden of comorbidities than AF patients, while the efficacy of PC in AFl was low. Patients should be initially managed with primary electrical cardioversion.