Background: Diverse treatment suggestions range from monitoring with duplex examinations to therapeutic anticoagulation (TA) for managing isolated calf muscle vein thrombosis (ICMVT). However, the small. sample sizes and low-level evidence provided by most studies in the literature mean that the benefits of promising new treatment protocols are unclear. Hence, this meta-analysis is intended to assess the efficacy and safety of TA for patients with ICMVT. Patients and methods: Articles comparing TA with no anticoagulation (NA) or no therapeutic anticoagulation (NTA) in patients with ICMVT were collected from PubMed, the Cochrane Library, EMBASE, and Web of Science. The risk ratio (RR) and 95% confidence interval (95% CI) were generated for each outcome of interest.The data were pooled using a random-effects or fixed effects model to evaluate differences in outcomes between the TA and control groups. Results: Five of 377 initially identified papers were included. One randomized controlled trial, one non-randomized controlled trial and three retrospective cohort studies (a total of 744 patients, 390 in the TA group and the remaining 354 in the NA or NTA group) were included in this meta-analysis. The occurrence of thrombosis progression was significantly less frequent in those who received TA compared with those receiving NTA (RR = 0.33, 95% CI 0.20 to 0.54, p < 0.01). The rate of complete recanalization was higher, albeit not significantly, in the TA group than in the NTA group (RR = 1.96, 95% CI 1.01 to 3.80, p = 0.05). None of the pooled outcomes were significantly different when comparing the TA and NA groups. Conclusions: This study suggests that TA may result in a significant reduction in the rate of thrombosis progression and a marginally significant increase in the rate of complete recanalization for patients with ICMVT. Further studies are needed to confirm these findings and clarify whether the benefits of TA outweigh the potential harm.