Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Background: The widening gap between innovations in the medical field and the dissemination of such information to doctors may affect the quality of care. Offline computer-based digital education (OCDE) may be a potential solution to overcoming the geographical, financial and temporal obstacles faced by doctors. Objective: Objectives: The objectives of this systematic review were to evaluate the effectiveness of OCDE compared to face-to-face learning, no intervention or other type of digital learning for improving medical doctors’ knowledge, cognitive skills and patient-related outcomes. The secondary objectives were to assess the cost-effectiveness of OCDE and any adverse, effects of the interventions. Methods: Methods: We searched the major bibliographic databases from 1990 to August 2017 to identify relevant articles and followed the Cochrane methodology for systematic reviews of intervention. Results: Results: Twenty-seven RCTs, one cluster RCT (cRCT) and one quasi-RCT were included in this review. The total number of participants was 1690 in addition to the cRCT, which included 24 practices. Due to heterogeneity of participants, interventions and outcomes meta-analysis was not feasible and results were presented as narrative summary. Compared to face-to-face learning, the effect of OCDE on knowledge gain is uncertain; (Ratio of the means (RM) range 0.95 to 1.17, eight studies 495 participants, very low grade of evidence). From the same comparison the effect of OCDE on cognitive skill gain is uncertain; (RM range 0.1 to 0.9, eight studies, 375 participants, very low grade of evidence). OCDE may have little or no effect on patients’ outcome compared to face-to-face education; (Two studies, 62 participants, low grade of evidence). Compared to no-intervention, OCDE may improve knowledge gain; (RM range 1.36 to 0.98, four studies, 401 participants, low grade of evidence). From the same comparison, the effect of OCDE on cognitive skill gain is uncertain, (RM range 1.1 to 1.15, four trials, 495 participants, very low grade of evidence). Only one cluster-randomized trial, involving 24 practices, investigated patients’ outcome in this comparison and shows no difference between the two groups with low-grade evidence. Compared to text-based learning, the effect of OCDE on cognitive skills gain is uncertain; (RM range 0.91 to 1.46, three trials with four interventions, 68 participants, very low-grade evidence). No study in this comparison investigated knowledge gain or patients’ outcomes. Only one study assessed the cost-effectiveness of the intervention and showed that OCDE was cost-effective when compared to face-to-face learning if the cost is ≤ Can$ 200. No trial evaluated the adverse effect of OCDE compared to other methods of education. Conclusions: Conclusions: The effect of OCDE compared to other methods of education on medical doctors’ knowledge and cognitive skill gain, is uncertain. OCDE may improve doctors’ knowledge compared to no-intervention but its effect on doctors’ cognitive skills is uncertain. OCDE may have little or no effect in improving patients’ outcome.