Randomized controlled trials (RCTs) have reported conflicting results on the impact of high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT) as the first-line treatment for patients with aggressive non-Hodgkin lymphoma (NHL). We performed a systematic meta-analysis to assess the efficacy of HDCT compared to conventional chemotherapy in patients with aggressive NHL with regard to overall survival (OS) at 3 years. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 11/2008) searches. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random effect model. Fourteen RCTs were identified that were published in full text and included a total of 2,413 patients. There was evidence that HDCT showed decreased OS (HR 1.20, 95% CI 1.05-1.37, P=0.006) at 3 years when compared with conventional chemotherapy. The variation in OS probabilities between studies was not statistically significant (test for heterogeneity, Q=10.14, df=13, P=0.683). Thus, our meta-analysis showed that HDCT in aggressive non-Hodgkin lymphoma had decreased overall survival outcome compared with conventional chemotherapy.