Tluszcz spent the first 10 years of his professional career at Arthur Andersen, ultimately becoming a partner in its business consulting practice before running its European venture capital fund. During this time he personally invested in a number of businesses including the Frederick Brewing Company which listed on the NASDAQ stock exchange.
In 2000 he founded Mangrove Capital Partners with Gerard Lopez and Hans-Jürgen Schmitz. He was the first investor in Skype, a telecoms business founded by Janus Friis and Niklas Zennström - who were at the time known for founding Kazaa, the peer-to-peer file sharing application. On 14 October 2005 Skype was acquired by eBay and Tluszcz was named as one of the most respected technology dealmakers globally by Forbes magazine.
In 2006, Tluszcz backed cloud-based web development platform Wix.com. He persuaded Wix.com not to sell when it was offered $400m and the company went on to float on NASDAQ in 2013. Its valuation as of August 2016 was $1.5bn. It remains the largest tech IPO to come out of Israel.
Tluszcz's firm looks at 2,000 startup deals a year but invests in just six. It has made approximately 100 investments into early-stage technology companies predominantly in Europe and Israel since it was founded in 2000. The company has raised four funds and has $750 million in "assets under management". In 2016 it had seven or eight startups in its portfolio enjoying rapid growth and worth over £100 million.
Tluszcz drew controversy in April 2015 when he stated that the majority of 'unicorn' companies (those claiming to be worth over $1bn) were in fact 'fakies'. Later in the year the technology industry experienced a significant correction with many highly prized companies seeing their values slashed. Having been valued at over $1bn in 2015, Shazam was acquired by Apple in 2017 in a deal thought to be worth $400m.