Assessment of prognostic indicators in patients with cystic fibrosis (CF) is important. The study's aim was to assess the relative contribution of gender, genetics and microbiology on survival in adults with CF. Adult patients were studied from 1995 to 2005 and data collected included FEV₁ (%predicted), body mass index (BMI), genetics, and microbiology. Data was available on 183 patients in 1995. Forty‐five patients died in the subsequent 10 years. Patients who died during the study had lower mean (SD) FEV₁ %predicted in 1995 when compared to those remaining alive, 41.5 (15.2)% versus 69.8 (23.2)% predicted, respectively, P < 0.001 and they had lower mean (SD) BMI in 1995, 19.2 (3.3) kg/m² in comparison to those remaining alive, 20.7 (3.4) kg/m², P = 0.008. The proportion of patients infected with Pseudomonas aeruginosa and Burkholderia cepacia complex was higher in the group who died during the study compared to those remaining alive, odds ratio 20.9 P < 0.0001 and 7.1 P < 0.0001, respectively. The presence of the ΔF508 homozygous mutation did not alter survival, P = 0.3. Patients infected with either P.aeruginosa or B.cepacia complex had reduced survival compared to those without infection, P = 0.01 and P < 0.0001, respectively. FEV₁% (P < 0.0001), infection with P.aeruginosa (P = 0.005) or B.cepacia complex (P = 0.03) were the only significant predictors of mortality. This study demonstrates adults who died were more likely to have worse lung function and be infected with either P.aeruginosa or B.cepacia complex. FEV₁% and infection with P.aeruginosa or B.cepacia complex were the most significant predictors of survival in adults with CF. Pediatr Pulmonol. 2007; 42:525–532. © 2007 Wiley‐Liss, Inc.