Patients with progressive glioblastoma (GBM) have a poor prognosis. Neutrophil/lymphocyte ratio (NLR), a host inflammatory marker, is prognostic in several solid tumors. The prognostic impact of either NLR, or time from first surgery for GBM to first progression (TTP), in patients undergoing second surgery, has not been assessed. Patients undergoing second surgery for GBM were retrospectively reviewed. Primary outcome was overall survival (OS) and Cox proportional hazard models were used to assess the prognostic value of baseline characteristics including TTP and NLR. Univariable and multivariable analysis (MVA) of OS from second surgery were performed using accelerated failure time Weibull model. Of 584 patients with GBM, 107 (18 %) underwent second surgery between 01/04 and 12/11. Patients who underwent second surgery had longer OS versus those having primary surgery alone; 20.9 versus 9.9 months (P < 0.001). Median OS from second surgery in patients with NLR ≤ 4 versus NLR > 4 was 9.7 versus 5.9 months (log rank P = 0.02). The NLR retained its prognostic significance for survival on MVA (time ratio [TR] 1.65, 95 % confidence interval [CI] 1.15–2.35, P < 0.01). No chemotherapy post second surgery (TR 0.23, 95 % CI 0.16–0.33, P < 0.001) portended worse survival. In patients undergoing second surgery, when TTP was ≤12 months, 12–24 months, or >24 months, median OS from second surgery was 7.2, 7.0 and 6.3 months, respectively (P = 0.6). A NLR > 4 prior to second surgery is a poor prognostic factor in GBM and later progression is associated with longer survival in patients but not in longer survival after second surgery.