Purpose Giant prolactinomas, which have extremely large sizes and high prolactin (PRL) values, are rarely seen. Although medical therapy is effective, surgical treatment is more frequently applied due to slightly lower response rates and compression symptoms. This study aimed to compare the medical and surgical treatment results in giant prolactinomas. Methods Thirty-nine patients who were followed up in our center for giant prolactinoma were included in the study, and the response rates of the patients were evaluated after the medical and surgical treatments. The treatment responses were compared in terms of tumor volume, PRL level, visual field, and pituitary function. Results The outcomes of the 66 treatment periods (medical n = 42; surgical n = 24) in 39 patients (mean age, 47.2 years; men, 89.7%) were evaluated. The most common presentations were hypogonadism and visual defects. The mean longest tumor diameter at diagnosis was 52.2 +/- 11.8 mm, and the median PRL levels were 5000 ng/mL. PRL level normalization was achieved in 69% with medical therapy, and a curative response was obtained in only two patients with surgery. Tumor volume reduction was 67% (no cure) in the medical and 75% (13% cure) in the surgical groups (p = 0.39). Improvement of visual field was 70.8% in the medical and 84.2% in the surgical group (p = 0.12). Conclusion In our study, it was observed that medical therapy was effective and safe in patients with giant prolactinomas. The use of surgical treatment should be limited to prolactinomas with compression or post-resistance to medical treatment in serious cases.