"Spontaneous" subclavian vein ("effort") thrombosis is usually related to extrinsic compression of the vein at the costoclavicular junction. Our experience with this entity over the past decade was reviewed with specific focus on the role of thrombolysis and our selection algorithm. All patients treated for this problem at the University of Rochester over the past decade were identified and records retrospectively reviewed. From 1996 to June 2006, a total of 34 patients with spontaneous complete occlusion of the subclavian vein documented by venography were treated, half with a history of an antecedent exertional factor. Catheter-directed thrombolysis prior to planned immediate thoracic outlet decompression (TOD) was performed in 26 patients, while TOD alone was performed in eight. Time since onset of symptoms was the major factor influencing the decision, being a mean of 5.5 days in the 26 referred for lysis but 1 month to many years in the group who underwent surgery alone. In patients undergoing lysis, flow was restored in 16 (62%), of whom nine had a residual lesion. All but two of the 26 who received thrombolysis then underwent TOD with or without angioplasty, and 13 underwent venous reconstruction as well (eight of the 16 in whom patency had been restored and five of eight in whom it had not). Patients not undergoing lysis were managed by TOD, with five (62%) undergoing decompression alone and three (38%) undergoing formal venous reconstruction. Thrombolysis was not attempted (eight) or unsuccessful (four) in all 12 patients whose symptoms had been present for more than 14 days at presentation. At mean follow-up of 33 months, symptom resolution was almost universal. Primary patency at 5 years was 84% in the thrombolysis group and 83% in the TOD-only group. In conclusion, the primary factor influencing treatment choice at our institution has been time since onset of symptoms. Patients presenting soon after symptom onset underwent thrombolysis followed by TOD, while patients presenting with chronic symptoms underwent TOD alone; in both cases venous reconstruction was based on residual findings after lysis. We have not had successful thrombolysis in a patient presenting with 14 days or more of symptoms. While optimal therapy cannot be defined based on this retrospective review, our algorithm resulted in excellent overall long-term patency and symptom relief.