Connective tissue disease (CTD) patients may suffer from pulmonary arterial hypertension (PAH), a serious complication, and anti-U1 ribonucleoprotein (RNP) antibodies can be used as a potential indicator for the development and prognosis of CTD-associated PAH (CTD-PAH). However, there are still some controversies; thus, a systematic review and meta-analysis were performed. We searched PubMed, Embase, Cochrane Library, and Scopus for eligible studies and assessed their quality using Newcastle–Ottawa scales or Agency for Healthcare Research and Quality indicators according to the type of research. Odds ratio (OR) was adopted as a measure of effect in risk factor analysis, and hazard ratio (HR) was adopted for prognostic factor analysis. Publication bias was evaluated using the Egger’s test. Thirteen studies were finally included. Anti-U1 RNP antibody was proved as a risk factor for PAH among CTD patients (OR = 5.30, 95%CI 2.96–9.48, p < 0.05) and a protective factor against mortality among CTD-PAH patients (HR = 0.55, 95%CI 0.36–0.83, p < 0.05). CTD patients with positive anti-U1 RNP antibodies are at high risk for PAH, so routine screening examinations, including echocardiography, are recommended. Additionally, anti-U1 RNP positivity has been linked to decreased mortality in patients with CTD-PAH.