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The purpose of this study was to assess the incidence, predictors, and prognostic clinical impact of atrial fibrillation (AF) over time after cavotricuspid isthmus (CTI) ablation of typical atrial flutter (AFL). This was a follow-up observational study using 408 patients who underwent CTI AFL ablation between 1998 and 2010. The relationships between the different predictors and the outcomes (AF, stroke, and death) were modeled by means of multistate Cox model analyses. The incident rate of AF per 100 person-years during follow-up was 10.2 (95 % CI 8.7–11.8). Prior AF and chronic obstructive pulmonary disease (COPD) were the only independent variables to predict AF occurrence in the population. Their hazard ratios (HRs) were 2.55 (95 % CI 1.84–3.52) and 1.56 (95 % CI 1.08–2.27), respectively. Patients who transitioned to AF had an increased risk of death by an HR of 2.82 (95 % CI 1.88–4.70) and an increased risk of stroke by an HR of 2.93 (95 % CI 1.12–8.90). Age, COPD, and heart failure (HF) were predictive factors of death by HRs of 1.05 (95 % CI 1.00–1.08), 2.85 (95 % CI 1.39–5.83), and 2.72 (95 % CI 1.15–6.40), respectively. Age, smoking, COPD, and HF were predictive factors of death in the group of patients with AF during follow-up. HRs were 1.07 (95 % CI 1.02–1.12), 2.55 (95 % CI 1.55–4.21), 7.60 (95 % CI 3.01–19.16), and 3.07 (95 % CI 1.18–7.95), respectively. The transition to AF after CTI AFL ablation was high during a long-term follow-up period and maintained over time. Prior AF and COPD were the primary predictors of transition to AF after CTI AFL ablation. Patients who transitioned to AF had an increased risk of stroke and a more than twofold mortality rate. These clinical implications make it necessary to investigate AF after CTI ablation.