Profitability is a motivational factor in any enterprise. The study compared the profitability of sole maize and maize/melon intercrop in Osun State. A purposive sampling technique was used and primary data collected with the aid of a structured questionnaire. Descriptive statistics, budgetary technique, inferential statistics and regression techniques were used to analyse the data collected. The majority of the respondents were active, male, had formal education and had less than 21 years of experience in cropping systems. The estimated net return to management was N59,323.83 per sole maize farmer or N37, 548.75 per hectare per year and N175,178.68 per farmer or N102, 832.17 per hectare for maize/melon. Budgetary analysis results showed that both sole maize and maize/melon intercrop were profitable. The multiple regressions for maize/melon intercrop revealed that 94.2% of variation in profit was obtained by independent variables in the model. The multiple regressions for the sole maize profit function revealed that 62.3% of variation in profit was obtained by independent variables in the model. The costs of input used, labour employed and quantity sold were the major determinants of profitability. The appropriate policies to enable the farmers to have access to inputs at a subsidised rate should be put in place.