The North-West (NW) region of Bangladesh is pivotal for the country’s agricultural development, mainly in producing irrigated Boro rice. However, increasing cost of irrigation water, fertilizers, labour and other inputs, and the spatio-temporal variation in actual yield, market price and profitability of rice, have added uncertainty to the sustainability of Boro rice cultivation. In this study, we evaluated the productivity, profitability, and prospect of Boro rice production using comprehensive field data collected directly from 420 farmers’ fields over two consecutive seasons (2015–16 and 2016–17), across seven geographically distributed locations in the NW region. We also analyzed the risk and return trade of popular Boro rice cultivars using Monte-Carlo simulation. The results show that there were significant (p≤0.05) variations in rice yield between sites, irrigation pump-types, and rice varieties, with Hybrid rice and BRRI dhan29 producing highest yields (6.0–7.5 t/ha). Due to different pricing systems, the cost of irrigation water varied from site to site and from year to year, but always comprised the highest input cost (20–25% of total production). The total paid-out cost, gross benefit, and gross income of rice significantly (p≤0.05) differed between sites, type of irrigation pumps, rice varieties, transplanting dates, and two cropping years. The variations in observed yield and profitability reveal considerable scope to improve rice production systems. Market variation in the price of rice affected overall profitability significantly. Probability and risk analysis results show that Minikit and BRRI dhan29 are the most stable varieties for yield and profitability. Hybrid rice, which has the maximum attainable yield among the cultivated rice varieties, also has the risk of negative net income. Based on the analysis, we discussed ways to improve yield and profitability and the prospect of Boro rice cultivation in the region. The study provides valuable information for policy-makers to sustain irrigated rice cultivation in both the NW region and nationally.