This study was conducted to retrospectively identify the prognostic factors that specifically predict survival rates of patients with aggressive non-Hodgkin's lymphoma who did not achieve a complete response (CR) to first-line therapy. Prognostic factors in terms of survival were analyzed in 76 adult patients with non-Hodgkin's lymphoma who had failed to achieve CR to first-line chemotherapy (CT) regimens administered at Istanbul University, Institute of Oncology, between February 1989 and October 1998. A total of 41 patients were female, and median age was 60 y (range, 18-87 y). Twenty-seven patients (35%) had primary refractory disease (stable disease + progressive disease). A partial response (PR) was demonstrated in 49 (65%). In all, 92% had been administered anthracycline on the basis of computed tomography findings. Of 27 patients with primary refractory disease, 20 died because of initial CT toxicity or disease progression. A total of 10 patients with primary refractory disease underwent second-line CT. CR was observed in only I of those patients. Of the 49 patients who had a PR to first-line therapy, 31 died because of disease progression. Of those patients, 14 underwent second-line CT. Four patients were observed to have a CR. Median overall survival (OS) in all patients was established at 15 mo (range, 11-19 mo), and 5-y OS was 25%. On the other hand, median OS in patients with primary refractory disease was 7.6 mo (range, 5.7-9.4 mo) and was observed to be 17.8 mo (range, 9.4-26.1 mo) in patients with a PR. The difference in survival rates between patients with primary refractory disease and those with a PR was significant (P=.005). Although median OS was 18.1 mo (range, 8.4-27.8 mo) in patients with intermediate-grade histology, it was 6.1 mo (range, 1-11.7 mo) in patients with high-grade histology (P=.001). As a result of univariate analysis, significant prognostic factors associated with OS included histologic grade (intermediate/high) (P=.001), response to initial therapy (primary refractory disease/PR) (P=.005), performance status (0-2/2-4) (P=.024), and International Prognostic Index risk groups (low/low intermediate/intermediate-high/high risk) (P=.004). Multivariate analysis revealed that independent prognostic parameters associated with OS included response to initial therapy (P=.009) and histologic grade (P=.001). Although prognosis is rather poor in patients with high histologic grade and primary refractory disease, patients with a PR have a slightly better prognosis.