BackgroundProblem-based learning (PBL) remains a valid and effective tool for small-group medical education. Using Virtual patients (VP) case simulation in PBL is a recognizable educational method that has successfully prepared students to focus learning on core information that uses realistic patient-based cases relating to everyday clinical scenarios. Using other modalities as the virtual patient in PBL instead of the paper-based methods remains debatable.This study aimed to evaluate the effectiveness of using VP case simulation mannequin in PBL versus the PBL in paper-based cases in improving the cognitive skills by comparing the grades of a multiple-choice question test and assess its ability to reach students' satisfaction using questionnaire with Likert survey instrument.MethodsThe study was conducted on 459 fourth-year medical students studying in the pulmonology module of the internal medicine course, Faculty of Medicine, October 6 University. All students were divided into 16 PBL classes and randomly divided into groups A and B by simple manual randomization. The groups were parallel with a controlled cross-over study between paper-based and virtual patient PBL.ResultsThe pre-test showed no significant difference between both, while post-test scores were significantly higher in both VP PBL cases 1 discussing COPD (6.25 ± 0.875) and case 2 discussing pneumonia (6.56 ± 1.396) compared to paper-based PBL (5.29 ± 1.166, 5.57 ± SD1.388, respectively) atp< 0.1 When students in Group A experienced PBL using VP in case 2 after paper-based PBL in case 1, their post-test score improved significantly. (from 5.26 to 6.56,p< .01). Meanwhile, there was a significant regression in the post-test score of the students in Group B when they experienced the paper-based PBL session in case 2 after using PBL using VP in case 1, (from 6.26 to 5.57,p< .01). Most of the students recommended using VP in PBL as they found VP was more engaging and inducing concentration in gathering the information needed to characterize the patient’s problem than in a classroom- paper-based cases session. They also enjoyed the teaching of the instructor and found it a suitable learning style for them.ConclusionImplementing virtual patients in PBL increased knowledge acquisition and understanding in medical students and was more motivating for students than paper based PBL to gather the needed information.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12909-023-04421-y.