Deep Vein Thrombosis (DVT): This is often the first consideration for unilateral leg swelling due to its relatively high prevalence and the potential for serious complications like pulmonary embolism. DVT typically presents with swelling, pain, and sometimes warmth of the affected leg.

Cellulitis: A bacterial infection of the skin and subcutaneous tissues, cellulitis can cause swelling, redness, warmth, and pain in one leg. It's a common condition that can be managed with antibiotics.
Lymphedema: This condition involves the abnormal collection of protein-rich fluid in the interstitial tissue, leading to swelling of one or more extremities. It can be primary (inherited) or secondary (due to surgery, infection, or other causes).
Venous Insufficiency: This condition occurs when the veins have problems returning blood from the legs back to the heart due to valve issues, leading to swelling, varicose veins, and skin changes.

Compartment Syndrome: A medical emergency characterized by increased pressure within a muscle compartment, leading to muscle and nerve damage. It presents with severe pain, swelling, and sometimes pallor or paresthesia of the affected limb.
Phlegmasia Cerulea Dolens: A severe form of DVT that causes significant swelling and cyanosis of the leg due to near-total occlusion of the venous outflow. It's a medical emergency requiring prompt intervention.
Ruptured Baker's Cyst: Although less common, a ruptured Baker's cyst can cause acute swelling of the leg, mimicking other conditions. It's essential to consider this diagnosis, especially in patients with a history of knee arthritis.

Lipedema: A chronic condition characterized by the abnormal growth of fat cells in the legs, leading to swelling and pain. It's often mistaken for lymphedema but does not typically respond to elevation.
Filarial Lymphedema (Elephantiasis): Caused by parasitic infections, this condition leads to severe swelling and disfigurement of the affected limb. It's rare in developed countries but should be considered in travelers or immigrants from endemic areas.
Klippel-Trenaunay Syndrome: A congenital condition characterized by vascular malformations, leading to swelling, varicose veins, and skin discoloration of the affected limb. It's a rare diagnosis that should be considered in patients with a long history of unilateral leg swelling.