Previous studies have reported that increased high-sensitive C-reactive protein (hs-CRP) levels are associated with an inflammatory state. This study investigated the association among hs-CRP, substrate properties, and long-term clinical outcomes after catheter ablation of atrial fibrillation (AF). A total of 137 patients with AF (54 ± 13 years) who underwent mapping and catheter ablation were included. The hs-CRP was measured before the first ablation procedure. The substrate properties (initiating triggers, biatrial mean voltage, and high-frequency sites) of the 2 atria and long-term outcome were investigated in patients in the low hs-CRP group (<75%, 2.92 mg/L) and high hs-CRP group (>75%, 2.92 mg/L). Patients with a higher hs-CRP were associated with an increased number of identified nonpulmonary vein ectopies (34.4% vs 17%, p = 0.034), lower mean left atrial (LA) voltage (1.72 ± 0.73 vs 1.92 ± 0.72 Hz, p = 0.045), and higher-frequency sites in the left atrium (71% vs 37%, p = 0.027). After a median follow-up period of 15 months, the single-procedure success rate (72% vs 53%, p = 0.008) and final success rate after multiple procedures (94% vs 81%, p = 0.02) were higher in the low hs-CRP group. In a multivariable regression model adjusted for other potential covariates, hs-CRP level (p = 0.021) and LA diameter (p = 0.032) were independent predictors of recurrence. In conclusion, baseline CRP levels before the first AF ablation procedure had an independent prognostic value in predicting long-term recurrence. Patients with a high hs-CRP level were associated with an abnormal LA substrate and high incidence of nonpulmonary vein AF sources.