Purpose To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas. Methods Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 & mu;g/L, tumor diameter & GE;40 mm] identified in the Swedish Pituitary Register 1991-2018. Results Eighty-four patients [mean age 47 (SD & PLUSMN;16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 & mu;g/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was & GE;10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 & mu;g/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively). Conclusion DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.