Ambulatory ultrasound-guided foam sclerotherapy (UGFS) for refluxing saphenous veins is considered a safe therapy. Venous thromboembolic complications after UGFS as well as after all other ambulatory ablative venous interventions are rarely reported. This paper reports a fatal pulmonary embolism (PE) following UGFS in combination with an extended phlebectomy, and questions what measures should be taken to minimize the risk for thromboembolic complications after these procedures. In the reported case (unsuspected), extensive non-occluding atherosclerosis as well as obesity in combination with use of an oral contraceptive might have contributed to the development of the PE while the use of a β-blocker might have increased its fatal course considerably. Routine measurement of the ankle-brachial pressure index reduces the risk for undetected atherosclerosis. It appears that ‘in the real world’ of ambulatory phlebological treatments thromboembolic complications are more common (2.4–4.7%) and appear accompanied by post-procedural mortality. It is concluded therefore that pharmacological thromboprophylaxis appears warranted in selected cases, perhaps even routine application could be considered. Attention is drawn to the highly thrombogenic but not uncommon combination of overweight and use of oral contraceptive. Apart from applying some form of pharmacological thromboprophylaxis, technical adaptations that might prevent or reduce spill over of foam into the deep venous system should be considered. Firstly, next to adherence to the generally accepted maximum of 10 mL of foam per session, it seems prudent to maximize the injected volume of foam per site. Secondly, it seems best to inject the foam in an elevated leg without groin compression. The concentration of the sclerosant does not appear decisive in this respect, although higher concentrations appear more effective and therefore might be injected in lower volumes without compromising efficacy.