Ralstonia species are Gram-negative bacilli that have increasingly been recognized as emerging nosocomial pathogens, particularly in immunocompromised hosts. Ralstonia pickettii is the most clinically important pathogen from the Ralstonia genus. Nosocomial outbreaks of Ralstonia pickettii infections brought about by the use of contaminated medical solutions, including saline, sterile water, as well as disinfectants, have been reported. There have been case reports of invasive infections with variable presentations. Here, we describe three cases of Ralstonia pickettii bacteremia during a period of one year in a tertiary care hospital in Karachi, Pakistan. The first case was a 76-year-old male, known case of type 2 diabetes mellitus (DM), hypertension, and amyotrophic lateral sclerosis, who presented with complaints of burning micturition, hematuria, and fever. The patient had a history of multiple hospital admissions in the recent past. His blood culture was found to be positive for Ralstonia pickettii. A computed tomography scan of the kidneys, ureter, and bladder (CT KUB) was suggestive of pyelonephritis. The patient improved on intravenous meropenem. The second case was a 47-year-old man, who was admitted with a gunshot injury to the neck, resulting in complete cervical cord resection and mild hydrocephalus with intraventricular hemorrhage. The patient had a prolonged intensive care unit (ICU) stay, which was complicated by ventilator-associated pneumonia with Acinetobacter and central line-associated bloodstream infection (CLABSI) with Ralstonia pickettii. He was treated with meropenem and colistin but continued to deteriorate and expired. The third case was a 46-year-old lady, known case of end-stage renal disease (ESRD), who was admitted with prosthetic valve endocarditis. She had a prolonged hospital stay complicated by CLABSI with Ralstonia pickettii, improved on meropenem, but later died due to fungemia. Ralstonia pickettii is an emerging cause of nosocomial infection in patients, particularly those with a prolonged hospital stay, and can cause invasive and severe infections.