The predominant technique used to draw blood for laboratory testing is a conventional straight needle attached to an evacuated tube system. However, alternative tools might be advantageous in exceptional circumstances. The use of butterfly devices has been traditionally discouraged for reasons of costs and due to the high risk of obtaining unsuitable samples, but there is no convincing evidence to support the latter indication. The purpose of this study was to compare results of hematological and clinical chemistry testing, after drawing blood into evacuated tubes, employing either a traditional 21-gauge straight needle or a 21-gauge butterfly device with 300-mm-grade polyvinyl chloride tubing. Blood samples and complete sets of data were successfully obtained for 30 consecutive outpatients. Of the 43 hematological and clinical chemistry parameters measured, means for paired samples collected by the two alternative drawing techniques did not differ significantly, except for serum sodium, white blood cells and platelets counts. Bland-Altman plots and limits-of-agreement analysis showed mean bias of between −7.2% and 1.7% and relative coefficients of variation ranging from 0.2% to 21.2%. The 95% agreement interval in the set of differences was acceptable and was mostly within the current analytical quality specifications for desirable bias. The rate of hemolysis in plasma was not statistically different between the two collection techniques. Taken together, the results of the present investigation suggest that, when a proper technique is used and within certain limitations, the butterfly device may be a reliable alternative to the conventional straight needle to draw blood for laboratory testing.