The impact of psychosocial variables on the survival of cancer is discussed controversially. In a prospective study, we investigated whether the quality of coping strategies are of prognostic value in newly diagnosed glioblastoma. In a prospective study, patients with newly diagnosed glioblastoma underwent audiotaped interviews immediately following surgery and before initiating radiochemotherapy. The patients’ coping strategies were then identified from each interview using the Ulm Coping Manual that describes 34 different coping strategies. An exploratory factor analysis was conducted to assess patterns of coping strategies that reflect the same underlying general coping mechanism (also known as factor). These factors are characterized by a set of highly correlated coping strategies. Patients who are highly associated (loaded highly on) with a specific factor were compared against those with low loadings. We compared overall survival (OS) between patients loading highly on a specific factor and those with negative loadings. A Cox regression analysis served to detect independent prognostic variables. Eighteen patients were eligible for interviewing. Six factors have been retained based on the amount of variation they explain in all coping strategies. Among those, factor 1 (F1) explained the overall highest amount of variation and was characterized almost exclusively by high loadings of active coping strategies, including taking the initiative, problem analysis, emotional support, optimism/hope, and active compliance with factor loadings ranging from 54%-92%. The high F1 loadings group had a particularly high median OS (24.1 months) as compared to the one with low F1 loadings (median OS, 10.6 months, p=0.0002). In a multivariable Cox regression analysis, F1 emerged as a prognostic factor (p<0.001) independent of canonical prognostic markers including age, Karnofsky performance score, extent of resection, and O6-methylguanin-DNA-methyltransferase (MGMT). Exploitation of coping mechanisms may offer a possible novel avenue for glioblastoma treatment. Further exploration in a larger trial is warranted.