Preventable drug-related morbidity (PDRM) indicators are operational measures of therapeutic risk management. These clinical indicators, which cover a wide range of drugs, combine process and outcome in the same instrument. They were developed in the US and have been validated for primary care settings in the US, UK and Canada. This study is part of a research programme; it aimed to determine a valid set of PDRM indicators for adult patients in primary care in Portugal. Face validity of 61 US and UK-derived indicators translated to Portuguese was preliminarily determined by means of a postal questionnaire using a purposive sample of four Portuguese pharmacists with different backgrounds. Preliminary content validity of indicators approved in the previous stage was determined by cross-checking each definition of PDRM with standard drug information sources in Portugal. Face and content validity of indicators yielded by preliminary work were then established by a 37 expert panel (20 community pharmacists and 17 general practitioners) using a two-round Delphi survey. Data were analysed using SPSS release 11.5. Nineteen indicators were ruled out in preliminary validation. Changes were made in the content of eight of the remaining 42 indicators; these were related to differences in the drugs being marketed and patterns of drug monitoring between countries. Thirty-five indicators were consensus approved as PDRM for adult patients in Portuguese primary care by the Delphi panel.