Background: Incomplete ascertainment of outcomes in randomized controlled trials (RCTs) is likely to introduce bias if reasons for unavailability of patient data are associated with the outcome of interest. The primary objective of our study was to assess the potential impact of loss to follow-up on the estimates of treatment effect. The secondary objectives were to describe (1) the reporting of loss to follow-up information, (2) the analytic methods used for handling loss to follow-up information, and (3) the extent of reported loss to follow-up. Methods: We conducted a systematic review of reports of 236 RCTs recently published in five top general medical journals. We included RCTs with statistically significant effect estimates with respect to primary outcomes that are patient-important and expressed as binary data. To assess the potential impact of loss to follow-up on the estimates of treatment effect we will, for varying assumptions about the outcomes of participants lost to follow-up (LTFU), calculate (1) the percentage of RCTs that lose statistical significance and (2) the mean change in effect estimate across RCTs. The different assumptions we will test are the following: (1) none of the LTFU participants had the event; (2) all LTFU participants had the event; (3) all LTFU participants in the treatment group had the event; none of those in the control group had it (worst case scenario); (4) the event incidence among LTFU participants (relative to observed participants) increased, with a higher relative increase in the intervention group; and (5) the event incidence among LTFU participants (relative to observed participants) increased in the intervention group and decreased in the control group. Results: We will present our results at the Cochrane Colloquium. Discussion: The results of this study may have important implications for clinical trialists, systematic reviewers and users of the medical literature.