Abstract Purpose In the multinational, randomized, double-blind, Phase 3 B2305 study of patients with Cushing’s disease (CD; ClinicalTrials.gov identifier NCT00434148), pasireotide substantially decreased urinary-free cortisol (UFC) levels, decreased mean corticotroph tumor volume, and improved clinical signs of disease. The current post hoc analysis further assesses the effects of pasireotide on corticotroph pituitary tumor volume. Methods Patients enrolled in the B2305 study had persistent or recurrent CD or newly diagnosed CD but were not surgical candidates. Enrollees were randomized to receive subcutaneous pasireotide, either 600-μg or 900-μg twice daily. Tumor volume was assessed independently at months 6 and 12 by 2 blinded radiologists and compared with baseline value and UFC response. Results Of 162 patients enrolled in the trial, 53 had measurable tumor volume data and were included in the post hoc analysis. Reductions in tumor volume were both dose and time dependent. Tumor volume reduction was more frequently observed at month 6 in the 900-μg group (75%) than in the 600-μg group (44%). Similarly, at month 12 (n = 32), tumor volume reduction was observed more frequently in the 900-µg group (89%) than in the 600-µg group (50%). Control of UFC levels was not required for reduction of tumor volume. No relationship was noted between baseline tumor size and change in tumor size. Conclusions Measurable decreases in pituitary tumor volume were observed in a large proportion of patients with CD and measurable tumor volume who were enrolled in the trial and treated with subcutaneous pasireotide; this decrease was not correlated with UFC control. ClinicalTrials.gov identifier NCT00434148.