No consensus or guideline has been established regarding the optimal timing of tissue resection after revascularization in patients with chronic limb-threatening ischemia (CLTI). This study aimed to compare early tissue resection and watchful waiting after revascularization regarding the outcomes of patients with CLTI. We searched PubMed, the Cochrane Library, and EMBASE for relevant randomized trials and observational studies published from their inception to May 1, 2024. In total, five articles were analyzed. The results showed that the early tissue resection group had a higher wound healing rate than the watchful waiting group (I2 = 26%, odds ratio [OR] = 2.80, 95% confidence interval [CI] 1.32 to 5.92, P = 0.007). However, the rate of major amputation was significantly higher in the early tissue resection group than in the watchful waiting group (I2 = 5%, OR = 1.48, 95% CI 1.18 to 1.86, P < 0.001), and wound recurrence rate in the early tissue resection group was relatively higher than that in the watchful waiting group (I2 = 0%, OR = 2.42, 95% CI: 0.99 to 5.93, P = 0.05). No statistical significance was found in the rate of postoperative mortality (I2 = 2%, OR = 0.99, 95% CI: 0.69 to 1.41, P = 0.94) and wound healing time (I2 = 97%, standardized mean difference = -105.92, 95% CI −232.96 to 21.13, P = 0.10) between the early tissue resection and watchful waiting groups. For patients without signs of infection, a watchful waiting strategy could reduce the risk of major amputation.