Objective: This study aimed to assess the scientific evidence on the efficiency of presurgical infant orthopedic appliances in patients with cleft lip and palate to shed light on a specific, contemporary discussion of whether the appliances have long-term advantages with respect to treatment outcomes.Design: A systematic review. Methods: Two literature surveys from the five electronic databases were performed with a 1-month interval. Randomized controlled trials and controlled clinical trials (controls had no presurgical infant orthopedics) that had followup periods of a minimum of 6 years were included in the study. The exceptions to the follow-up limit were studies related to feeding and parent satisfaction.Results: Of the 319 articles retrieved in the literature surveys, 12 were qualified for the final analysis. The level of evidence of these articles ranged from 1b to 4. Eight randomized controlled trials and four controlled clinical trials were available on eight treatment outcomes. The longest follow-up period of the randomized controlled trials was 6 years. No randomized controlled trials were found on active presurgical infant orthopedic appliances and on nasoalveolar molding appliances.Conclusions: Based on the results, presurgical infant orthopedic appliances have no long-term positive effects on seven of the eight studied treatment outcomes in patients with cleft lip and palate. More randomized controlled trials need to be done to have evidence regarding the effects of presurgical infant orthopedics in different surgical protocols. Also, the encouraging results about the effect of nasolaveolar molding appliances on nasal symmetry have to be supported by future randomized controlled trials.