Purpose: To evaluate the impact of gender and year at surgery on clinical presentation and postoperative outcomes in acromegaly. Methods: Retrospective review of patients operated between 1994 and 2016 to compare presentation and outcomes in groups defined by gender and year of surgery. Kaplan–Meier survival analyses with a composite endpoint (recurrence, reoperation, and radiation) were used for gender comparison and Youden indices for biochemical remission rates changes during study period. Results: Primary indications for evaluation were phenotype, neurological symptoms, incidentaloma, hypogonadism, and galactorrhea. At surgery, men (N = 54) were younger (43.6 ± 12.7 years) than women (N = 58, 48.7 ± 12.3, P = 0.04). Male:female ratios before and after age 50 were 1.4 and 0.6 respectively. Men had higher mean IGF-1 levels (874 ± 328 vs 716 ± 296, P < 0.01) and smaller tumors (1.8 ± 1.3 cm vs 2.3 ± 1.5, P = 0.04). Postoperative remission rates were comparable (51% men, 56% women) and inversely associated with cavernous sinus invasion and GH levels. Women had longer mean follow-up (5.2 ± 3.4 years vs 3.6 ± 3.6 men, P = 0.02) and longer endpoint-free survival (P < 0.01). At last follow-up, 89.6% women and 70% men had normal IGF-1 levels (P = 0.03). Postoperative remission rates were higher in patients operated after February 15, 2011 (67.35 vs 43.5% previously, P = 0.01). In late vs early surgery group, physical changes as main indication for screening decreased (54 vs 30%, P < 0.01), while incidentaloma and hypogonadism increased. Median GH levels were lower in late vs early surgery group (P = 0.03). Conclusion: We demonstrate gender-specific characteristics and an evolving spectrum of clinical presentation with implications for earlier diagnosis and personalized management of acromegaly.