Background: Early mobilization is one of the essential components of enhanced recovery after surgery (ERAS) pathways and has been shown to reduce complications and optimize patient outcomes. However, the effect of early mobilization for patients who undergo trans-femoral cardiac catheterization and the time for optimal mobilization timing remains controversial. We aimed to identify the safety of early mobilization and provide the optimum timing for early mobilization for patients undergoing trans-femoral cardiac catheterization. Methods: We searched MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases of systematic reviews, CINAHL, SCOPUS, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Chinese Science and Technology Periodical Database (VIP) comprehensively for randomized controlled trials associated with early mobilization, to explore its effects on patients after a trans-femoral cardiac catheterization. The risk of bias and heterogeneity of studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and I{}^2 index, respectively. The comprehensive Meta-analysis (CMA) was adopted to perform the meta-analysis. Results: We identified 14 trials with 2653 participants. Early mobilization was associated with significant decrease in back pain (mean difference (MD) = 0.634, 95% CI: 0.23–1.038; p = 0.002), especially in patients receiving instruction for early mobilization in 3 h~4 h versus 5 h~6 h (MD = 0.737, 95% CI: 0.431–1.043; p = 0.000) and 12 h versus 24 h (OR = 5.504, 95% CI: 1.646–18.407; p = 0.006) categories. The results of subgroup analysis also showed a significant risk reduction in urinary retention by early mobilization in 12 h versus 24 h (OR = 5.707, 95% CI: 1.859–17.521; p = 0.002) category. Conclusions: Early mobilization has not been shown to increase the risk of bleeding, hematoma, pseudoaneurysm, urinary retention, and pain at the puncture site after trans-femoral cardiac catheterization. Early mobilization is a practical initiative in ERAS, and it may be safe and feasible to advance the mobilization to 2 h~4 h.