Use of telehealth assessments for toddlers at increased likelihood of autism spectrum disorder (ASD) began prior to the global COVID-19 pandemic; however, the value of telehealth assessments as an alternative to in-person assessment (IPA) became clearer during the pandemic. The Naturalistic Observation Diagnosis Assessment (NODA™), previously demonstrated as a valid and reliable tool to evaluate asynchronous behaviors for early diagnosis, was enhanced to add synchronous collection of behaviors to assist clinicians in making a differential diagnosis of ASD. This study was conducted to validate the information gathered through NODA-Enhanced (NODA-E™) as compared to a gold standard IPA. Forty-nine toddlers aged 16.0-32.1 months of age, recruited through community pediatric offices and a tertiary ASD clinic, participated in both NODA-E and IPA assessments. There was high agreement between the two assessment protocols for overall diagnosis (46 of 49 cases; 93.6%; [kappa] = 0.878), specific diagnostic criteria for social communication and social interaction (SCI; range 95.9-98%; [kappa] = 0.918-0.959), and for two of four criteria specified for restricted and repetitive behaviors (RRB; range 87.8-98%; [kappa] = 0.755 and 0.959). There was lower agreement for two subcategories of RRBs (range 65.3-67.3%; [kappa] = 0.306 and 0.347). NODA-E is a tool that can assist clinicians in making reliable and valid early ASD diagnoses using both asynchronous and synchronous information gathered via telehealth and offers an additional tool within a clinician's assessment toolbox.