Background—Direct-to-consumer (DTC) sequential aligners promote “teeth straightening” at a low cost and with added patient convenience. DTC sequential aligners have risen in popularity among the general public and sparked debate among dental professionals. Dental professionals argue that using these aligners without an in-person diagnosis and treatment planning protocol set by a licensed dentist or orthodontist may lead to adverse effects on teeth and surrounding structures. The objective of this study is to describe adverse clinical events associated with the use of DTC sequential aligners as reported in the Food and Drug Administration’s Manufacturer and User Facility Device Experience (FDA MAUDE) database. Methods—We searched the MAUDE database from 1 January 2010 to 31 December 2020 for the product code of ‘NXC’ (sequential aligners). The year, type of adverse event, reporter occupation, and event description were noted. Results—651 reports associated with sequential aligners were found, of which 104 were related to DTC sequential aligners. Fifty-four adverse events were reported in 2019. From the event description, 41.3% comprised bite problems, 29.8% comprised orofacial pain, and 26.6% of patients had some form of periodontal sequelae. Furthermore, 69.2% of the patients followed up after an adverse event with a dentist not associated with DTC aligners. Conclusions—The use of DTC sequential aligners without dental supervision has led to oral health problems, as documented in the MAUDE database. Commonly reported adverse events include bite problems, pain, sensitivity, and periodontal disease, and some adverse events are irreversible.