OBJECTIVES: Adherence measurements developed for mono-pharmacotherapy, such as the Medication Possession Ratio (MPR), are not appropriate to calculate adherence to poly-pharmacotherapy. These standard metrics tend to over/under estimate adherence in patients with treatment regimens consist of multiple medications. This study aimed to develop a new method for calculating medication adherence in patients using poly-pharmacotherapy by linking prescribing and administration data of general practitioners (GPs), and pharmacy dispensing records. METHODS: We evaluated existing methods for calculating medication adherence from dispensing data records. Standards for estimating medication adherence to poly-pharmacotherapy were defined. A new approach to calculate adherence to poly-pharmacotherapy was developed. RESULTS: The proposed new approach for estimating medication adherence to poly-pharmacotherapy consists 2 novel indexes (the multiple-Medications Prescribing Ratio [mMPrR] and the multiple-Medications Possession Ratio [mMPR]) and a medication adherence visualization tool (the Prescription and Medication Possession Graph [PMPG]). The mMPrP is for calculating adherence to prescribe medications and the mMPR to (re)fill prescriptions. The PMPG completes the mMPrR and the mMPR with indicating medication adherence in time and allowing to evaluate tendencies in the observation period. Among other parameters, number of medications, therapeutic indication, treatment length (e.g., chronic conditions requiring periodic treatment), dosage, generic and therapeutic switching, therapeutic duplication, and oversupply were considered for the construction of mMPrP, mMPR and PMPG. The face-validity of the approach were demonstrated with four illustrative cases (i.e., generic switching, therapeutic duplication, oversupply, periodic treatment). CONCLUSIONS: The proposed new method enables a more accurate measurement of adherence to poly-pharmacotherapy compared to MPR. The mMPrP, the mMPR and the PMPG would allow GPs to identify substantial adherence issues during consultations and could be routinely used to enhance medication adherence in countries where GPs have access to pharmacy dispensing records of their patients such as in Hungary.