Transdiagnostic internet-delivered cognitive behavioral therapy (iCBT) for emotional disorders has been shown to be effective in specialized care in the short term. However, less is known about its long-term effects in this specific setting. In addition, predictors of long-term effectiveness may help to identify what treatments are more suitable for certain individuals. This study aimed to analyze the long-term effectiveness of transdiagnostic iCBT compared with that of treatment as usual (TAU) in specialized care and explore predictors of long-term effectiveness. Mixed models were performed to analyze the long-term effectiveness and predictors of transdiagnostic iCBT (n=99) versus TAU (n=101) in public specialized mental health care. Outcomes included symptoms of depression and anxiety, health-related quality of life (QoL), behavioral inhibition and behavioral activation, comorbidity, and diagnostic status (ie, loss of principal diagnosis) from baseline to 1-year follow-up. Sociodemographic characteristics (sex, age, and education) and clinical variables (principal diagnosis, comorbidity, and symptom severity at baseline) were selected as predictors of long-term changes. Compared with baseline, transdiagnostic iCBT was more effective than TAU in improving symptoms of depression (b=-4.16, SE 1.80, 95% CI -7.68 to -0.67), health-related QoL (b=7.63, SE 3.41, 95% CI 1.00-14.28), diagnostic status (b=-0.24, SE 0.09, 95% CI -1.00 to -0.15), and comorbidity at 1-year follow-up (b=-0.58, SE 0.22, 95% CI -1.00 to -0.15). From pretreatment assessment to follow-up, anxiety symptoms improved in both transdiagnostic iCBT and TAU groups, but no significant differences were found between the groups. Regarding the predictors of the long-term effectiveness of transdiagnostic iCBT compared with that of TAU, higher health-related QoL at follow-up was predicted by a baseline diagnosis of anxiety, male sex, and the use of psychiatric medication; fewer comorbid disorders at follow-up were predicted by older age and higher baseline scores on health-related QoL; and fewer depressive symptoms at follow-up were predicted by baseline diagnosis of depression. However, this pattern was not observed for baseline anxiety diagnoses and anxiety symptoms. The results suggest that transdiagnostic iCBT is more effective than TAU to target depressive symptoms among patients with emotional disorders. Anxiety symptoms remained stable at 1-year follow-up, with no differences between the groups. Results on predictors suggest that some groups of patients may obtain specific gains after transdiagnostic iCBT. Specifically, and consistent with the literature, patients with baseline depression improved their depression scores at follow-up. However, this pattern was not found for baseline anxiety disorders. More studies on the predictor role of sociodemographic and clinical variables in long-term outcomes of transdiagnostic iCBT are warranted. Future studies should focus on studying the implementation of transdiagnostic iCBT in Spanish public specialized mental health care. ClinicalTrials.gov NCT02345668; https://clinicaltrials.gov/ct2/show/NCT02345668.