There are limited data on the management of pulmonary arterial hypertension (PAH) in the elderly; therefore, this analysis compared the safety and efficacy of tadalafil between patients >65 and <65 years old. This was a post hoc analysis of the randomized, double-blind, placebo-controlled phase 3 Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST-1) study. Patients who completed the 16-week study or who discontinued because of clinical worsening and were not receiving tadalafil 40 mg were eligible for a long-term, open-label extension study. Adverse events (AEs) and efficacy outcomes were assessed in patients >65 versus <65 years old, and the dose dependency of common AEs was determined. Twenty-eight percent (112 of 405) of patients were >65 years of age (mean in this subset, 72 ± 5 years). Compared with younger patients, elderly patients were more likely to be World Health Organization functional class III/IV (75% vs. 65%, respectively) and to have lower exercise capacity as assessed by 6-minute walk distance (6MWD; mean, 299 vs. 366 m). Compared with placebo, tadalafil increased 6MWD by a mean of 35 and 43 m in patients >65 and <65 years, respectively. Common AEs (including headache, dyspepsia, and myalgia) were similar in both groups and tended to decrease in incidence with longer treatment duration. No differences in AEs were observed between elderly patients who received tadalafil 20 or 40 mg. In conclusion, the safety and efficacy of tadalafil for treatment of PAH are similar between elderly patients and patients < 65 years old.