Paecilomyces variotii is a ubiquitous environmental saprophyte with worldwide distribution. Commonly found in soil and decomposing organic material [1, 2], P. variotii can also be isolated from drinking water [3] and indoor and outdoor air [4–6]. In immunocompetent hosts, P. variotii has been reported as a cause of locally invasive disease including prosthetic valve endocarditis [7, 8], endophthalmitis [9, 10], rhinosinusitis [11, 12], and dialysis-associated peritonitis [13, 14]. In contrast, disseminated infections are more commonly reported in immunocompromised patients, including those with chronic granulomatous disease [15], solid malignancy [16], acute leukemia [17], lymphoma [18], multiple myeloma [19], and after stem cell transplant for myelodysplasia [20]. In 1 case series examining invasive infections by non-Aspergillus molds, P. variotii was the most common cause after Fusarium spp. [21]. Here, we present the case of an immunocompetent patient with extensive intravascular infection involving prosthetic material. We describe successful induction therapy with combination antifungals and extended suppression with posaconazole with clinical quiescence and eventual normalization of serum fungal biomarkers.