Objective. To assess the potential effectiveness and medical costs of three common strategies to manage Stage IB2 squamous cell carcinoma of the cervix (CXCA). Methods. A decision analysis model compared three strategies to manage Stage IB2 CXCA: (1) radical hysterectomy with pelvic and para-aortic lymphadenectomy followed by tailored chemoradiation therapy for high-risk patients (RHYST); (2) primary chemoradiation therapy for all patients (CTRT); and (3) neoadjuvant chemotherapy followed by radical hysterectomy and tailored chemoradiation therapy for high-risk patients (NAC). Results. RHYST was the least expensive strategy with a cost of 284 Million (M) per 10,000 women and a 5-year disease free survival (5-DFS) of 69%. Both NAC and CTRT had similar 5-DFS (69.3% and 70%, respectively); however, both NAC and CTRT were more expensive than RHYST at 299 M and 508 M, respectively. This translated into a higher cost-effectiveness ratio for NAC and CTRT ($43,197 and $72,613, respectively) when compared to RHYST ($41,212). NAC yielded 30 additional survivors compared to RHYST but at a cost of $499,783 per survivor. CTRT was more effective than RHYST with 100 additional survivors but at a substantial cost of $2,240,000 per survivor. Conclusions. RHYST is the most cost-effective strategy to manage Stage IB2 CXCA and would be favored in settings where resources are limited. Although NAC and CTRT are reasonable treatment strategies, policymakers must be willing to spend approximately $500,000 per additional survivor (NAC) or $2.2 M per additional survivor (CTRT). © 2005 Elsevier Inc. All rights reserved.