Purpose Differences in clinical outcome are still unclear between primary and secondary bladder carcinoma in situ. We compared the clinical outcomes of primary and secondary carcinoma in situ, and identified predictive factors. Materials and Methods We retrospectively analyzed the records of 476 patients with high grade cTis, including 221 with primary and 255 with secondary carcinoma in situ, from 1990 to 2008 at a high volume cancer center after transurethral resection and intravesical bacillus Calmette-Guerin therapy. End points were time to progression to invasive disease (cT1 or higher) or radical cystectomy before progression, and progression to muscle invasive disease (cT2 or higher) or radical cystectomy before progression. We used Cox proportional hazards regression models. Results Patients with primary carcinoma in situ responded significantly more within 6 months of bacillus Calmette-Guerin than those with secondary carcinoma in situ (65% vs 39%, p <0.001). In the primary vs secondary groups the 5-year cumulative incidence of progression to cT1 or higher was 43% (95% CI 36–51) vs 32% (95% CI 27–39) and for progression to cT2 or higher it was 17% (95% CI 12–23) vs 8% (95% CI 5–13). On multivariate analysis primary carcinoma in situ was significantly more likely to progress to cT1 or higher (HR 1.38, 95% CI 1.05–1.81, p = 0.020) and to cT2 or higher, or radical cystectomy (HR 1.72, 95% CI 1.27–2.33, p = 0.001). We found no significance for age, gender or response to bacillus Calmette-Guerin as outcome predictors. Median followup was 5.1 years. Conclusions Patients presenting with primary carcinoma in situ have a worse outcome than those with secondary carcinoma in situ, suggesting a need to differentiate these 2 entities in the treatment decision process.