Acute pyelonephritis is not considered a common cause of renal vein (RVT) and inferior vena caval thrombosis (IVCT). Apart from malignancy, RVT is not an uncommon condition amongst patients with nephrotic syndrome, most commonly seen in patients with membranous glomerulonephritis. However, RVT occurring in association to acute pyelonephritis is rare. Clinically, it is difficult to distinguish between acute pyelonephritis and RVT because both present with fever, flank pain, and hematuria. We report a case of acute pyelonephritis with RVT and IVCT with underlying hyperhomocysteinemia. The patient was treated with systemic anticoagulation, antibiotics, and B complex therapy. At 3 months follow-up, there was complete resolution of thrombus but the left kidney was nonfunctioning.