The goal of this study was to evaluate the incidence, predictors, and clinical outcomes of thrombus propagation in patients with isolated calf muscle venous thrombosis (CMVT). This retrospective observational study included all consecutive hospitalized patients who were diagnosed with isolated CMVT between January 1, 2022, and August 1, 2024. Data on demographics, comorbidities, laboratory biomarkers, and management strategies were collected. The primary end point was the incidence of thrombus propagation (defined as either a previously localized thrombi within the muscular calf veins that was found to extend to the axis calf veins or proximal veins of the ipsilateral extremity or as a thrombus that had clearly extended but remained confined to the muscular calf veins) during follow-up. Secondary end points included the incidence of venous thromboembolism (VTE) recurrence (defined as the formation of a new thrombus [ipsilateral or contralateral deep vein thrombosis or pulmonary embolism] confirmed by imaging during follow-up after complete resolution of the original CMVT), bleeding events, rehospitalization, and death. Among the 459 patients included in this study, the incidence of CMVT propagation was 8.7% (n = 40). Independent predictors of thrombus propagation were immobilization (odds ratio [OR]; 3.06 [95% confidence interval, 1.04-8.99]; P = .042), history of VTE (OR, 4.31 [95% CI, 1.42-13.05]; P = .010), and elevated D-dimer level (OR, 1.06 [95% CI, 1.02-1.09]; P = .003). The mean time to propagation was 9.3 ± 5.2 days. VTE recurrence rates were 2.5% (n = 1) in patients with propagation and 1.7% (n = 7) in patients without propagation (P = .702). Major bleeding events occurred in 5.0% of patients (n = 2) with propagation and in 3.1% of patients (n = 13) without propagation (P = .519). During the follow-up period, no patients were rehospitalized or died owing to VTE events. Thrombus propagation in patients with isolated CMVT is uncommon and generally not fatal. Predictors of CMVT propagation include immobilization, history of VTE, and elevated D-dimer level. These findings may help to identify patients with a significant risk of CMVT propagation.