Objective: Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the determinants of surgical remission in these tumors. Methods: We searched PubMed to identify eligible studies reporting postoperative remission in patients treated with transsphenoidal surgery for prolactinoma. Primary outcomes included postoperative remission, follow-up remission, and recurrence. Postoperative and follow-up remission were defined as normoprolactinemia at <1 year and >1 year after operation, respectively. Recurrence was defined as hyperprolactinemia after initial normalization of prolactin levels. Odds ratios (ORs) were calculated, stratified by radiologic size, tumor extension, and tumor invasion, and analyzed using a random-effects model meta-analysis. Results: Thirty-five studies were included. Macroadenomas were associated with lower rates of postoperative remission (OR, 0.20; 95% confidence interval [CI], 0.16–0.24) and lower rates of remission at follow-up (OR, 0.11; 95% CI, 0.053–0.22). Postoperative remission was less likely in tumors with extrasellar or suprasellar extension (OR, 0.16; 95% CI, 0.06–0.43) and tumors with cavernous sinus invasion (OR, 0.03; 95% CI, 0.01–0.13). Female gender and absence of preoperative dopamine agonist treatment were also associated with higher remission rates. Across the included studies, there was considerable heterogeneity in each primary outcome (postoperative remission, I2 = 94%; follow-up remission, I2 = 86%; recurrence, I2 = 68%). Conclusions: Transsphenoidal surgery for prolactinomas may be particularly effective in small, noninvasive, treatment-naive tumors and may provide a viable first-line alternative to dopamine agonist therapy in such patients.