The inability of farmers to comply with essential precautions in the course of spraying agrochemicals remains a policy dilemma, especially in developing countries. The objectives of this paper were to assess compliance of cocoa farmers with agrochemical safety measures, analyse the factors explaining involvement of cocoa farmers in the practice of reusing agrochemical containers and wearing of personal protective equipment (PPE). Data were collected with structured questionnaires from 667 cocoa farmers from the Centre and South West regions in Cameroon. Data analyses were carried out with Probit regression and Negative Binomial regression models. The results showed that average cocoa farm sizes were 3.55 ha and 2.82 ha in South West and Centre regions, respectively, and 89.80% and 42.64% complied with manufacturers’ instructions in the use of insecticides. Eating or drinking while spraying insecticides and fungicides was reported by 4.20% and 5.10% of all farmers in the two regions, respectively. However, 37.78% and 57.57% of all farmers wore hand gloves and safety boots while spraying insecticides in the South West and Centre regions of Cameroon, respectively. In addition, 7.80% of all the farmers would wash agrochemical containers and use them at home, while 42.43% would wash and use them on their farms. Probit regression results showed that probability of reusing agrochemical containers was significantly influenced (p < 0.05) by region of residence of cocoa farmers, gender, possession of formal education and farming as primary occupation. The Negative Binomial regression results showed that the log of number PPE worn was significantly influenced (p < 0.10) by region, marital status, attainment of formal education, good health, awareness of manufacturers’ instructions, land area and contact index. It was among others concluded that efforts to train farmers on the need to be familiar with manufacturers’ instructions and use PPE would enhance their safety in the course of spraying agrochemicals.