Compression therapy, prescribed as elastic compression stockings, is the cornerstone in the management of post-thrombotic syndrome. The effectiveness of elastic compression stockings has recently been called into question in a large randomized placebo-controlled trial. The findings however may be less contradictory than assumed and presented. The mechanistic substrate for the effectiveness of compression therapy is based on its ability to counteract venous hypertension, which is a central aspect in the pathophysiology of post-thrombotic syndrome. Nevertheless, despite elastic compression stockings a significant percentage (20–50%) of patients develops post-thrombotic syndrome, suggesting that there are other factors to be considered next to compression. Every patient has an individual baseline risk value, constituted of non-modifiable and modifiable risk factors (i.e. age, sex, bodyweight etcetera). Straining patients at risk is therefore crucial. Exploring additional or alternative forms of therapy is desirable as well since these are in addition to the risk factors, costs aspects and quality of life, puzzle pieces in the management of post-thrombotic syndrome, which once pieced together enables multifactorial yet individualized therapy.