Objective: To identify the factors associated with important (≥50%) variation in awareness and practice of evidence-based obstetric interventions in an African setting where we have previously reported poor awareness and use of evidence-based reproductive interventions. Design: Cross-sectional analysis of data from our Reproductive Health Interventions Study. Setting: North-west province, Cameroon, Africa. Population: Health workers including obstetricians, other physicians, midwives, nurses and other staff providing reproductive care. Main outcome measures: Prevalence ratios (PR) of uniform awareness and practice of four key evidence-based obstetric interventions from the World Health Organization Reproductive Health Library (WHO RHL): antiretrovirals to prevent mother-to-child transmission of HIV/AIDS, antenatal corticosteroids for prematurity, uterotonics to prevent postpartum haemorrhage and magnesium sulphate for seizure prophylaxis. Methods: Comparisons of descriptive covariates, applying logistic regression to estimate independent relationships with awareness and use of evidence-based interventions. Results: A total of 15.5% (50/322) of health workers were aware of all the four interventions while only 3.8% (12/312) reported optimal practice. Evidence-based awareness was strongly associated with practice (PR = 15.4; 96% CI: 4.3-55.0). Factors significantly associated with awareness were: attending continuing education, access to the WHO RHL, employment as an obstetrician/gynaecologist and working in autonomous military or National Insurance Fund facilities. Controlling for potential confounding, working as an obstetrician was associated with increased awareness (adjusted prevalence odds ratio [aPOR] = 8.3; 95% CI: 1.3-53.8) as was median work experience of 5-15 years (aPOR = 2.0; 95% CI: 1.0-3.8). Internet access was associated with increased practice (aPOR = 3.4; 95% CI: 1.0-11.8). Other potentially important variations were observed, although they did not attain statistical significance. Conclusions: Several factors including obstetric training and continuous education positively influence evidence-based awareness and practice of key obstetric interventions. Confirmation and application of this information may enhance the effectiveness of programmes to improve maternal and perinatal outcomes. © RCOG 2006.