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This study examined the profitability of herbicide weed control in yam-maize-soybean enterprise, factors influencing it, as well as the problems encountered by the farmers using this weed control measures. The study was conducted in Bwari Area Council of the Federal Capital Territory (FCT) in the Northern Guinea Savanna agro-ecological zone of Nigeria, between August, 2015 and January, 2016. Data were collected from 60 randomly selected farmers using a structured questionnaire, and analyzed using descriptive statistics, net income, gross margin model and multiple regressions. Result shows that the enterprise was dominated by male farmers (97%) with 88% of them married and had an average household size of 7 persons. The respondents were educated with average farm size of 4 ha. The gross revenue was ₦1,062,695.08 per hectare, with net income of ₦280,118.615 and the return per naira was 1.36, implying that for every naira spent in the enterprise the farmer expects a return of ₦1.36. The gross margin ratio estimate was 1.69, and this result implied that for every ₦1 realized from the sales of yam, maize and soybean the farmer had ₦1.69 kobo left over to cover basic variable costs as well as profit. Lack of credit facilities, high cost of labour, environmental effects and high cost of herbicide were the major problems encountered by the farmers. Level of education, farm size, household size, farming experience, use of herbicide was all positively related to profit and significant at 5% probability level. Polices that would favour herbicide subsides and credit facilities for farmers in this agro-ecology zone will be a strong incentive for increased productivity and profitability.