Introduction. Pituitary adenomas are the most frequent intracranial tumors of the central nervous system. Except for prolactinomas, surgery is the treatment of choice.Aim: to assess the percentage of patients with persistent disease after surgery and to identify independent predictors of persistent disease.Material and methods. Ambispective multicenter observational study. Data were collected from The Molecular Registry of Pituitary Adenomas (REMAH). Univariate and multivariate analysis were performed in 128 patients with histologically confirmed adenomas who underwent transsphenoidal surgery between 2009 and 2015 in hospitals from Madrid, with at least one month of follow-up.Results. During follow-up, persistent disease was observed in 50.8% of patients (radiological 30.7%, biochemical 2.4%, both 14.2%), especially in nonfunctioning tumors. Factors significantly associated with persistent disease in the univariate analysis were age, male gender, previous hypopituitarism, large tumor diameter and microscopic transsphenoidal surgery (p <0.05). Independent predictors of persistent disease in multivariate analysis were: patients over 76 years old, a greater tumor diameter, multiple hypopituitarism and microscopic transsphenoidal surgery (p <0.05).Conclusion. Age, tumor size, previous hypopituitarism and the type of surgical technique were independent predictors of persistent disease. These factors could be useful for clinicians in the follow-up of patients to better establish monitoring and treatment algorithms.