Based on the thermodynamic calculations, the universal secondary cooling structure, and the specific water rate for round blooms continuous casting in various diameters were investigated with a 2D heat transfer model. Results indicated that extension of the secondary cooling zone along casting direction significantly lowered the surface temperature recovery after the water cooling, though little influence on the recovering rate. The universal secondary cooling structure for the continuous casting of round blooms in diameters from 280 to 350 mm was optimized by appropriately extending the length of secondary cooling zone. The target unbending temperature was 908 °C for steel 16MnNb due to the thermodynamic calculation. To the optimized universal secondary cooling structure, the optimal specific water rates were 0.35 and 0.25 L kg−1 for the continuous casting of round blooms 280 and 350 mm in diameter, respectively. The present study had been applied to real production, resulting in round blooms in good quality, and contributing to the efficiency and flexibility of round blooms continuous casting process.