OBJECTIVES: There is an increased need to conduct international chart review studies (chart reviews) since healthcare databases with required information are not consistently available. Chart reviews offer an alternative for the effective capture and analysis of real-world patient-level data on patient characteristics and outcomes, treatment patterns, treatment effectiveness and safety.  For successful implementation, awareness of significant multi-national design and operational considerations is necessary.  METHODS: A critical review of 13 recent chart reviews conducted in Europe and North America on treatment patterns, clinical outcomes and/or drug utilization and safety was undertaken. Design and operational challenges, opportunities, and learnings are delineated.  RESULTS: All studies collected data retrospectively. Two studies collected certain information prospectively. Four studies were categorized as post authorization safety studies. Therapeutic areas varied across the studies with 8 studies being in oncology. Sample size ranged from 20-2,000 patients, number of countries ranged from 1-6, and number of sites ranged from 4-375.  All studies included at least 1 European country. Across studies, key design considerations include confirming the eligibility and study periods that permit evaluations of recent care patterns yet allow for sufficient follow-up time, case ascertainment and sampling frame methodologies, and safety reporting in the context of retrospective source data.  Additionally, key operational considerations include balancing science and practicality in site selection, ambiguous multinational ethical/regulatory requirements, country variations for informed consent, data collection designed to minimize site burden, and effective yet cost-efficient site management for quality data.   CONCLUSIONS: International chart reviews are proving to be an effective methodology for capturing tailored, patient-level data. These studies can be used to address a myriad of research objectives. Through conduct and assessment of recent chart reviews, the design and operational considerations involved can be understood with opportunities for improvement learned. These lessons will help for better planning and overcoming these challenges.