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Cocoa from Ghana is of premium quality but non-recommended farmer practices could impact negatively on the quality of cocoa beans. Therefore, this study sought to determine the effect of some agricultural practices that could affect the quality of cocoa beans from four districts in two ecological zones. Treatments included samples of cocoa beans from the two ecological zones produced using either recommended or non-recommended practice. Offinso and Tepa in the Ashanti region as well as Goaso and Sankore districts in Brong Ahafo region were purposively selected from each of the ecological zones for more accurate results. The study was both field survey and laboratory work. The survey involved the use of structured questionnaire to obtain primary data from the farmers and purchasing clerks. The laboratory work was a 4×3 factorial experiment in completely randomized design with three replications. Results from the survey were analysed with SPSS and showed that majority of the farmers practiced harvesting at correct interval, fermentation, drying, disease and pest control which affected the quality of cocoa beans. However, majority of farmers did not practice pruning, fertilisation, proper storage, hence affecting quality. The laboratory results indicated that practices in Offinso and Tepa in the Forest Transition Zone of Ashanti Region had significantly (P≤ 0.05) better influence on the physical, chemical, and microbial quality of cocoa beans than Goaso and Sankore in the Deciduous Forest Zone of Brong Ahafo region. Also, there were significant differences (P≤ 0.05) in the four districts for percentage mouldy beans, slaty, pH, fat content, mould count and faecal coliform. Moreover, recommended farmer practices had a significant effect on the final quality of beans than non-recommended farmer practices at the various districts. It is, therefore, concluded that fermentation, drying, harvesting and Disease and pest control, which were the key practices, significantly influenced the physical, chemical and microbial quality of cocoa beans irrespective of the ecological zones.