ObjectiveTo summarize diagnostic strategies of unilateral lower limb swelling. MethodThe clinical data of 357 patients hospitalized with unilateral lower limb swelling from March 2013 to October 2014 in our department were analyzed retrospectively. ResultsThree hundred and seven (86.0%) patients were admitted to hospital within 2 weeks since the symptom onset (acute swelling), the most common cause (281 cases) was lower extremity deep vein thrombosis (DVT), other causes included infection (11 cases), hematoma (7 cases), lymphatic obstruction (4 cases), iliac vein compression syndrome (2 cases), pelvic tumor compression (1 case), arteriovenous fistula (1 case). Etiology for chronic swelling contained lower extremity DVT (33 cases), arteriovenous fistula (5 cases), lymphatic obstruction (5 cases), Klippel-Trenaunay syndrome (3 cases), pelvic tumor compression (3 cases), iliac vein compression syndrome (1 case). Up to 60.5% (26/43) lower limb swelling which were not due to DVT had histories of misdiagnosis as DVT. Nine cases of lymphatic obstruction were secondary to malignant tumor itself or the sequel of treatment. Three hundred and thirty-eight (94.6%) patients were received lower limb doppler ultrasound, while 308 patients (91.9%) were diagnosed. Fifty-nine patients needed further CT venography (CTV) or CT angiography (CTA), 10 patients were received radionuclide lymphoscintigraphy to be diagnosed. ConclusionsAlthough DVT is the main cause of unilateral lower limb swelling, the lower limb swelling which is not due to DVT is frequently misdiagnosed and belatedly treated. Considering the complexity and reciprocal overlapping for the etiology of lower limbs swelling, developing a appropriate diagnosis strategy is important. Apart from history taking and physical examination, color doppler ultrasound for the lower limb is suggested to be the preferred imaging examination mean. Pelvic cavity screening for occupancy lesions and iliac vein should be evaluated synchronously if possible. For cases which can't be diagnosed by ultrasound, CTV, CTA, or radionuclide lymphoscintigraphy could be important supplement to assist the diagnosis.