The aim of this study was to present a case of deep vein thrombosis (DVT) and pulmonary embolism (PE) after an intrathecal baclofen bolus test. The study was carried out at a tertiary care rehabilitation center in Italy, and it reports a case of a 65-year-old woman affected by primary lateral sclerosis, with lower limb spasticity, who underwent an intrathecal baclofen bolus trial. After a 100 microg baclofen test, she developed hypotension and oxygen desaturation lasting two days. A Doppler ultrasonography was positive for DVT, and echocardiography confirmed the diagnosis of PE. A Doppler ultrasonography performed before the test was negative. This is the first report in the literature of DVT and PE after an intrathecal baclofen bolus trial. Clinicians and patients should be informed that the intrathecal baclofen bolus trial procedure could be associated with rare but important risks such as DVT and PE, and they should be alert in recognizing potentially life-threatening complications.