Objective Researchers have no empirically based search stopping rule when looking for potentially relevant articles for inclusion in systematic reviews. We tested a stopping strategy based on capture–mark–recapture (CMR; i.e., the Horizon Estimate) statistical modeling to estimate the total number of articles in the domain of clinical decision support tools for osteoporosis disease management using four large bibliographic databases (Medline, EMBASE, CINAHL, and EBM reviews). Study Design and Setting Retrospective evaluation of the Horizon Estimate using a systematic review of randomized controlled trials (RCTs) at two levels of article screening: title and abstract (1,246 potentially relevant articles) and full text (42 potentially relevant articles). Results The CMR model suggests that the total number of potential articles was 1,838 for the first level of screening, and 49 for the full-text level. The four databases provided 68% of known articles for the first level of screening and 81% for full-text screening. Conclusions The CMR technique can be used in systematic reviews to estimate the closeness to capturing the total body of literature on a given topic. More studies are needed to objectively determine the usefulness of Horizon Estimates as a stopping rule strategy for systematic review searching.