Oral targeted therapies play an important role in the treatment of pulmonary arterial hypertension (PAH). Several new oral agents have emerged for PAH in recent years. However, whether they provide a survival advantage is still not clear. This meta-analysis aimed to assess the efficacy and safety of oral targeted therapies, especially on predefined clinical worsening events. Trials were searched in the Cochrane Library, EMBASE, and PUBMED databases through June 2018. We calculated risk ratios for dichotomous data and weighted mean differences with 95% confidence intervals (CI) for continuous data. Twenty-five trials with a total of 6847 participants were included in the meta-analysis. Oral targeted therapies were associated with significant risk reduction in clinical worsening compared with placebo (relative risk [RR] 0.64; 95% CI = 0.58–0.70; P < 0.001). This reduction in risk was driven by reduction in non-fatal endpoints, including PAH-related admissions to hospital (RR = 0.66; 95% CI = 0.56–0.76; P < 0.001), treatment escalation (RR = 0.43; 95% CI = 0.28–0.66; P < 0.001), and symptomatic progression (RR = 0.55; 95% CI = 0.48–0.64; P < 0.001), but not by reduction of mortality (RR = 0.87; 95% CI = 0.68–1.12; P = 0.215). Oral targeted therapies were also associated with improvement in 6-min walk distance (26.62 m; 95% CI = 20.54–32.71; P < 0.001) and World Health Organization functional class (RR = 1.36; 95% CI = 1.20–1.54; P < 0.001). The results of this meta-analysis showed the benefits of oral treatments on clinical worsening events in PAH. However, these oral agents did not show any survival benefit in the short-term follow-up.