Objectives: Periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome is characterized by recurrent episodes of fever. Attenuated disease severity was considered in patients with Mediterranean fever (MEFV) gene variations. Corticosteroids are highly effective in controlling the symptoms but usually cause more frequent episodes. Frequent fever episodes either initiated after the steroid therapy or as an initial disease characteristics are the most challenging feature. Methods: Sixty-seven patients were prospectively followed from September 2015 to January 2018. MEFV variants were searched in all patients. Colchicine therapy was initiated in patients with MEFV variants and with shortened intervals after the initiation of steroid therapy. Results: Heterozygous MEFV gene variants were detected in 23 patients (34.3%). Higher exon 10 allel frequencies were found in patients with frequent fever episodes. Among 26 patients with increased episodes, colchicine treatment decreased the number of the episodes in 8 of 10 (80%) and 4 of 16 (25%) patients with and without variants, respectively (p = 0.022). Fever duration decreased (3.26 +/- 1.38 vs. 1.57 +/- 0.57 days, p < 0.001) at the third month of therapy in variant(+) patients. Conclusion: In variant positive patients colchicine prophylaxis reduced the duration of attacks at the third months of therapy. Shortened intervals due to steroid therapy were increased at the sixth months of colchicine therapy.