Despite abundant tools and systems claiming support for knowledge work, many have failed to be accepted by users. Designing information systems (ISs) for knowledge work is a challenging task, but results on how knowledge work is actually performed is scarce and so are instruments that help to translate results into artefacts useful for IS design. This paper takes the perspective of work practices and proposes an approach to collaboratively study and analyze practices of knowledge work. The approach uses stereotypes of users, called personas, in order to inform IS design activities. The persona concept is enriched with respect to behaviour concerning practices of knowledge work. Furthermore, a procedure for selecting primary personas out of a set of personas is suggested based on cluster analysis. The approach is illustrated with the case of a collaborative ethnographically-informed study of seven organizations in four European countries. The proposed approach is the more suitable, the more innovative, big and diverse the project, the planned product, the developers and the target group are. User-centered design activities benefit from personas by reduced effort for involving end-users and a continuous focus on characteristics of critical users and their way of performing practices of knowledge work.