Objective About 41 million people aged ≥18 years reported lifetime use of cocaine, and 5.4 million people reported having used cocaine in 2019. We aim to identify trends of cocaine use, manifestations, concomitant drug use, and financial burden on health care among hospitalized patients. Methods We utilized National Inpatient Sample from years 2006-2018. Patients with age ≥18 years, admitted to the hospital with a diagnosis of cocaine abuse, dependence, poisoning, or unspecified cocaine use were included in the study. We used ICD-9 Clinical Modification (CM) and ICD-10-CM codes to retrieve patient samples and comorbid conditions. The primary outcome was the trend in cocaine use among hospitalized patients from the year 2006 to 2018. Cochran-Mantel-Haenszel test was used to assess the significance of trends. Results In the year 2006, the prevalence of cocaine abuse among hospitalized patients was 10,751 per million with an initial decline to 7,451 per million in 2012 and a subsequent increase to 11,891 per million hospitalized patients in 2018 with p =0.01. The majority of patients admitted were older than 50 years (43.27%), and a greater percentage of patients were males. All ethnicities showed a rising trend in the use of cocaine except for Native Americans. Cardiovascular effects, neuropsychiatric and infectious manifestations in hospitalized patients with cocaine abuse showed a consistent increase from year 2006 to 2018 with p <0.001. Conclusions There is a recent uptrend in cocaine use among hospital admissions in the US from 2006 to 2018 with an increased rate of systemic manifestations. This highlights the impact of cocaine use on the health system and the dire need to address this growing problem.