BackgroundCurrent guidelines for evaluating cleft palate treatments are mostly based on two-dimensional (2D) evaluation, but three-dimensional (3D) imaging methods to assess treatment outcome are steadily rising.ObjectiveTo identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate.Data sourcesLiterature was searched using PubMed (1948–2012), EMBASE (1980–2012), Scopus (2004–2012), Web of Science (1945–2012), and the Cochrane Library. The last search was performed September 30, 2012. Reference lists were hand searched for potentially eligible studies. There was no language restriction.Study selectionWe included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample size had at least one cleft type. Only primary publications were included.Data extractionIndependent extraction of data and quality assessments were performed by two observers.ResultsFive hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements; therefore, only a systematic review could be conducted. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time.ConclusionAvailable evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate it.Systematic review registrationInternational Prospective Register of Systematic Reviews, PROSPERO CRD42012002041