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Aim: This study determined the prevalence and key determinants of burnout among nurses and midwives in Kumasi, Ghana. Design: Hospital‐based cross‐sectional study. Method: A questionnaire was used to obtain data from 391 nurses and midwives at a tertiary hospital in Kumasi, Ghana using simple random sampling. Results: About 84.4% of the participants were females. The majority of the study participants experienced low burnout for all dimensions (58% in emotional exhaustion, 55.5% poor personal accomplishment and 38.3% depersonalization). Multiple regression analysis revealed that high emotional exhaustion was independently predicted by post‐graduate education (β = 6.42, p =.003), lack of support from management (β = 2.07, p =.024), dislike for leadership style, (β = 3.54, p <.001) and inadequate number of staff (β = 2.93, p =.005). Age (β = 0.35, p =.004), lack of support from management (β = 1.60, p =.012), and inadequate number of staff (β = 1.49, p =.034) independently predicted high depersonalisation. Female sex (β = 4.36, p <.001) and years of practice (β = −0.26, p <.001) independently predicted low personal accomplishment. [ABSTRACT FROM AUTHOR]