Prognostic genetic testing can guide treatment decisions and predict outcomes for patients with chronic lymphocytic leukemia (CLL). Among 1494 patients with CLL treated in the community setting, prognostic genetic testing was infrequently performed and the outcomes were inferior for patients with unfavorable-risk disease. This highlights the importance of prognostic testing for patients with CLL to guide treatment and improve outcomes. Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy. In the present analysis of the Connect CLL Registry (ClinicalTrials.gov identifier, NCT01081015), a prospective observational cohort study of patients treated across 199 centers, the patterns of prognostic testing and outcomes of patients with unfavorable-risk genetics were analyzed. From 2010 to 2014, 1494 treated patients were enrolled in the registry by line of therapy (LOT), and stratified by the results of cytogenetic/fluorescence in situ hybridization (FISH) testing into 3 risk levels: unfavorable (presence of del17p or del11q), favorable (absence of del17p and del11q), and unknown. Cytogenetic/FISH testing was performed in 861 patients (58%) at enrollment; only 40% of these patients were retested before starting a subsequent LOT. Of those enrolled at the first LOT, unfavorable-risk patients had inferior event-free survival compared with favorable-risk patients (hazard ratio, 1.60; P = .001). Event-free survival was inferior with bendamustine-containing regimens (P < .0001). Event-free survival did not differ significantly between risk groups for patients treated with ibrutinib or idelalisib in the relapse/refractory setting. The predictors of reduced event-free survival included unfavorable-risk genetics, age ≥ 75 years, race, and treatment choice at enrollment. The present study has shown that prognostic cytogenetic/FISH testing is infrequently performed and that patients with unfavorable-risk genetics treated with immunochemotherapy combinations have worse outcomes. This underscores the importance of performing prognostic genetic testing for all CLL patients to guide treatment.