The usual practice of design of riser tubes of natural circulation boilers is with an assumption of uniform furnace heat flux. Using the uniform diameter of riser tubes inside the furnace zone is also very common. The effect of peripheral nonuniform distribution of furnace heat flux on thermo-hydraulic characteristics and design of the riser downcomer circuit of a natural circulation boiler is presented here for the first time. As the riser tubes are exposed under substantially high heat flux, the tubes containing water-steam mixture are vulnerable and susceptible to overheating, particularly at high flux zone. From systematic analysis, it is proposed that using different diameters and the number of riser tubes at various sections can overcome the early occurrence of tube dry-out. An appropriate two-phase flow model is developed with flow regime mapping, tube wall temperature calculation, and identification of possible dry-out. The peripheral nonuniform distribution of furnace heat flux is implemented analytically in the model by introducing a distribution parameter estimated from the actual furnace data. Results reveal that with an average heat flux of 150 kW/m2, the dry-out occurs near a riser tube height of 44 m for a typical 210 MW capacity boiler. However, considering the nonuniform heat flux variation, the dry-out appears near a height of 32 m and 73 m for higher and lower heat flux zone, respectively. The present analysis shows that the implementation of larger size and lower size diameter of riser tubes, respectively, in higher and lower heat flux regions has a 9.45 % cost-benefit compared to the usual design practice with a consideration of uniform diameter tube and heat flux. The present work concludes that instead of using uniform tube diameter with average heat flux assumption, the use of different diameter of tubes in different heat flux zone not only avoid the early onset of possible dry-out but also has a cost-benefit.