Background: Orthodontic patients wearing fixed appliances are susceptible to traumatic dental injuries during a wide range of sporting activities. This randomized clinical trial investigated wearability and preference of mouthguards during sporting activities in patients undergoing orthodontic treatment with fixed appliances. Methods: A prospective three-arm crossover randomized clinical trial conducted in the UK. Thirty patients in active orthodontic treatment with fixed appliances undertaking at least 120 minutes of contact sport per 6-8-week observation period were randomly assigned to one of six mouthguard allocation sequences consisting of three mouthguard types: (MG1) custom-made laboratory constructed, (MG2) mouth-formed OPRO® Gold Braces, and (MG3) pre-fabricated Shock Doctor® Single Brace. Patients completed a nine-outcome 100-mm visual analogue scale (VAS) questionnaire relating to mouthguard wearability during sport. Once feedback was completed, subjects were allocated the next mouthguard in the sequence. At study-end, subjects were asked to identify their preferred mouthguard. Results: Twenty-four patients (median age = 13; inter-quartile range 12-14.5 years) completed n = 72 follow-up questionnaires with most playing rugby union or field hockey. Considering VAS score as a continuous variable, for comfort, stability, hardness, ability to breathe, ability to not cause nausea, and inclination to chew, MG2 performed better than MG3. For categorization of VAS score into low (less than 80 mm) or high (at least 80 mm) wearability, for comfort, stability, ability to not cause nausea, and inclination to chew, MG1 and MG2 also rated superior to MG3. Patients preferred MG1 overall. Conclusions: This randomized clinical trial found that during contact sport patients in fixed appliances reported superior wearability for custom-made and mouth-formed mouthguards in comparison to pre-fabricated. Overall, patients preferred custom-made mouthguards.