High-intensity focused ultrasound (HIFU) is widely used for skin rejuvenation and tightening. The aim of this study was to determine the safety and efficacy of HIFU for face and neck rejuvenation. A systematic search of peer reviewed articles published before December 2017 was performed using Medline, Web of Science, and Scopus databases. Retrieved studies were screened, and clinical trials or follow-up studies which were evaluated the effect of HIFU on rejuvenation treatments of face and neck area were included. Risk of bias for each study was assessed and was reported. Safety and efficacy variables, which were reported more often in papers, were included in meta-analysis. Seventeen studies involving 477 participants were included in the analysis. Meta-analysis showed moderate improvement as scores of 2.74 (95% CI 2.06-3.43) and 2.68 (95% CI 1.92-3.45), out of 5 maximum score, for objective improvement score and subjective satisfaction score, respectively. Meta-analysis of mean pain score, assessed by a 0-10 Likert score, was 4.2 (95% CI 4.27-5.19). Edema and erythema showed considerable heterogeneity, and no hyperpigmentation was reported by included studies. Included studies used multiple and different outcome variables with different scoring at various time points. Long follow-up was not reported by majority of studies. HIFU is safe procedure in short term and has a moderate effect on rejuvenation of face and neck areas.