Objectives: To determine the clinical features, outcomes, and factors associated with the emergence of colistin-resistant gram-negative rods isolated from patients admitted to intensive care units. Methods: This cross-sectional study was conducted at the intensive care units of Liaquat National Hospital, from April 2019 to February 2020. Gram-negative rods resistant to colistin with minimum inhibitory concentrations ⩾ 4 mcg/mL according to Clinical and Laboratory Standards Institute criteria as reported in cultures were included. Clinical, demographical data and treatment given were recorded and analyzed using SPSS version 25. Results: A total of 93 patients were included; 58.1% were males. The mean age of patients was 59.48 ± 18.36 years. The most common organism isolated was Klebsiella pneumoniae (91.4%). The most common specimen was the tracheal (62.4%). Ventilator-acquired pneumonia was seen in 38.7%. The most common co-morbid disease seen in patients was diabetes (41%); 77% had a symptomatic infection and were treated with a combination of 2 or more antibiotics, most commonly meropenem plus fosfomycin. The most common susceptible antibiotics were fosfomycin (72%) and tigecycline (50.5%). Mean intensive care unit stay and total duration of hospital stay were prolonged (16.83 ± 12.93 and 23.34 ± 17.52 days, respectively). Forty-eight (62.3%) patients with symptomatic infection with colistin-resistant isolates were treated and discharged, and mortality was seen in 23 (29.9%). A significant association was found between mortality and symptomatic infection, endotracheal intubation with mechanical ventilation (p = 0.003), and a prolonged hospital stay of >20 days (p = 0.041). Conclusion: Colistin-resistant gram-negative rods pose a significant problem especially in developing countries because of limited therapeutic options. Stringent infection control and comprehensive antimicrobial stewardship programs are needed to overcome this challenge.