ObjectiveWe aimed to determine the key predictors of perinatal deaths using machine learning models compared with the logistic regression model.DesignA secondary data analysis using the Kilimanjaro Christian Medical Centre (KCMC) Medical Birth Registry cohort from 2000 to 2015. We assessed the discriminative ability of models using the area under the receiver operating characteristics curve (AUC) and the net benefit using decision curve analysis.SettingThe KCMC is a zonal referral hospital located in Moshi Municipality, Kilimanjaro region, Northern Tanzania. The Medical Birth Registry is within the hospital grounds at the Reproductive and Child Health Centre.ParticipantsSingleton deliveries (n=42 319) with complete records from 2000 to 2015.Primary outcome measuresPerinatal death (composite of stillbirths and early neonatal deaths). These outcomes were only captured before mothers were discharged from the hospital.ResultsThe proportion of perinatal deaths was 3.7%. There were no statistically significant differences in the predictive performance of four machine learning models except for bagging, which had a significantly lower performance (AUC 0.76, 95% CI 0.74 to 0.79, p=0.006) compared with the logistic regression model (AUC 0.78, 95% CI 0.76 to 0.81). However, in the decision curve analysis, the machine learning models had a higher net benefit (ie, the correct classification of perinatal deaths considering a trade-off between false-negatives and false-positives)—over the logistic regression model across a range of threshold probability values.ConclusionsIn this cohort, there was no significant difference in the prediction of perinatal deaths between machine learning and logistic regression models, except for bagging. The machine learning models had a higher net benefit, as its predictive ability of perinatal death was considerably superior over the logistic regression model. The machine learning models, as demonstrated by our study, can be used to improve the prediction of perinatal deaths and triage for women at risk.