Background: Subsyndromal symptoms have been recognized as relevant in the course and outcome of bipolar disorder (BD) patients. Nevertheless, their definition and cutoff points on current depression and mania scales are uncertain. The recently defined International Society for Bipolar Disorders (ISBD) operational criteria for the assessment of the course and outcome of bipolar illness have never been tested until now. Methods: A naturalistic longitudinal follow-up study of up to 5 years included a cohort of 317 DSM-IV-TR BD outpatients. For the first time, we assessed the proportion of visits in different affective states using the ISBD criteria. Secondarily, we compared the results with those obtained applying other cutoff points. Results: Patients were symptomatic in 39.1% (95% CI 35.3–42.9) of the visits. Subsyndromal symptoms, primarily subsyndromal depression, were present in 15.9% of patients (95% CI 13.4–18.4). No significant differences were found between bipolar I patients and bipolar II patients. There were differences in the total percentage of visits in euthymia depending on the cutoff points (p < 0.05). Conclusions: Applying ISBD criteria, bipolar patients have significant clinical morbidity and are often symptomatic, both with threshold symptoms and with subthreshold symptoms, especially with depression. The chosen cutoff points modify the apparent results. Limitations: The cutoff points used have not been validated. Psychopharmacologic treatments were naturalistic.