Background: Whether the diagnostic approach for celiac disease (CD) can really affect quality of life (QoL) and dietary compliance remains controversial. Aims: This study aimed to evaluate QoL and compliance to gluten-free diet (GFD) in adolescents/young adults diagnosed with CD through a screening strategy during childhood compared to age-matched CD patients diagnosed by case-finding and to assess whether follow-up at a referral center for CD influences compliance and QoL. Materials and Methods: Thirty-seven CD patients who were diagnosed by screening programs (SC-group) and 38 age-matched CD patients diagnosed due to symptoms (CF-group) were enrolled. Patients were asked to answer a questionnaire on QoL, dietary compliance, and follow-up care for CD. Results: Twenty-nine patients of the SC-group (median age 18.0 years, interquartile range [IQR] 16.0-19.0) and 31 patients of the CF-group (median age 17.0 years, IQR 15.5-18.0) completed the questionnaire. No significant difference relating adherence to the GFD and QoL was shown between the two groups. The majority (93.5%) of CF-group regularly had annual follow-up at a referral center compared to 37.9% of the SC-group (p < 0.001). Conclusion: The diagnostic strategy does not seem to impact QoL and dietary compliance. However, implementation of follow-up might still be necessary for patients identified through screening.