Timely identification of a cow’s reproduction status is essential to minimize fertilityrelated losses on dairy farms. This includes optimal estrus detection, pregnancy diagnosis and the timely recognition of early embryonic death and ovarian problems. On farm milk progesterone (P4) analysis could indicate all of these fertility events simultaneously. However, milk P4 measurements are subject to a large variability both in terms of measurement errors and absolute values between cycles. In this study, an innovative monitoring system based on milk P4 using the principles of synergistic control is presented. Instead of using filtering techniques and fixed thresholds, the present system employs an individually updated online model to describe the P4 profile, combined with a statistical process control chart to identify the cow’s fertility status. The inputs for the latter are the residuals of the online model, corrected for the concentration-dependent variability which is typical for milk P4 measurements. The objective of this paper is to present the developed methodology and give an indication of its use on farm. To this end, the system was validated on the P4 profiles of 38 dairy cows. The positive predictive value for luteolysis followed by estrus was 100%, meaning that the monitoring system picked up all estrous periods identified by the experts. Pregnancy or embryonic mortality was characterized by the absence or detection of luteolysis following an insemination, respectively. For thirteen cows, no luteolysis was detected by the system within the 25-32 days after insemination, indicating pregnancy, which was confirmed later by rectal palpation. It was also shown that the system is able to cope with deviating P4 profiles having prolonged follicular or luteal phases, which may suggest the occurrence of cysts. Future research is recommended for optimizing sampling frequency, prediction of the optimal insemination window and the establishment of rules to detect problems based on deviating P4 patterns.INTERPRETIVE SUMMARY. Progestrone-based online fertility monitoring. Adriaens.Milk progesterone based monitoring systems can be valuable for indicating fertility events in dairy cows, as the evolution of the milk progesterone levels can be related to acyclicity, estrus, pregnancy, and ovarian problems. We developed a system to translate raw progesterone measurements into clear information for the farmer, based on a mathematical model and a statistical control chart. In this way, a detailed image of a cow’s reproduction status on-farm can be obtained and fertility-related losses minimized.