Object Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q). Methods The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors. Results Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q. Conclusions In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.