Background: Clinical reasoning skills are essential for medical practice. Problem-based collaborative learning via the internet might prove useful in imparting these skills. Aim: This randomized study assessed whether web-based learning (WBL) is superior to face-to-face problem-based learning (PBL) in the setting of a 6-week cardio-respiratory course. Methods: During winter term 2007/08, all 148 fourth-year medical students enrolled in the 6-week course consented to be randomized in small groups to diagnose a patient complaining of dyspnoea either using a virtual collaborative online module or a traditional PBL session. Clinical reasoning skills were assessed by means of a key feature examination at the end of the course. Results: No significant difference between the mean scores of both study groups was detected ( p ¼ 0.843). In virtual learning groups, costs for diagnostic tests were significantly correlated to the number of contributions to online group discussions (r ¼ 0.881; p ¼ 0.002). Evaluation data favored traditional PBL sessions over virtual collaborative learning. Conclusion: While virtual collaborative learning was as effective as traditional PBL regarding the acquisition of clinical reasoning skills, it was less well accepted than traditional PBL. Future research needs to determine the ideal format and time-point for computer-assisted learning in medical education.