The median survival age for females with cystic fibrosis (CF) is approximately 3 years younger than for males. We tested whether earlier acquisition of Pseudomonas aeruginosa (PA) by female CF patients or the greater impact of this organism on their lung disease, or both, contribute to their poorer survival. PA infection status, survival, pulmonary function tests, and chest X-ray scores from patients who were followed at our center for at least 2 years with a minimum of three respiratory cultures per year were analyzed (n = 848). The median age of chronic infection with mucoid PA was 1.7 years earlier in females than in males. Patients infected with mucoid PA had poorer survival, chest X-ray scores, and pulmonary function tests than patients who had either no Pseudomonas species or only the nonmucoid phenotype. Acquisition of mucoid PA was associated with an accelerated rate of decline in pulmonary function. However, the rate of change of pulmonary function after mucoid PA infection was similar for males and females. Moreover, even among patients who had only the mucoid form or only the nonmucoid form, males had better percent predicted forced expiratory volume in 1 sec and better survival. Therefore, factors in addition to earlier acquisition of mucoid PA may contribute to the poorer survival of female CF patients.