To determine whether a 4-a-side handball (HB) game is an appropriate aerobic stimulus to reach and potentially enhance maximal oxygen uptake (V˙O2max), and whether heart rate (HR) is a valid index of V˙O2 during a handball game. Nine skilled players (21.0±2.9 yr) underwent a graded maximal aerobic test (GT) where V˙O2max and HR−V˙O2 relationship were determined. V˙O2, HR and blood lactate ([La]b) were recorded during a 2×225s (interspersed with 30s rest) 4-a-side handball game and were compared to those measured during an 480-s running intermittent exercise (IE). Mean V˙O2 tended to be higher in handball compared to IE (93.9±8.5 vs. 87.6±7.4% O2max, p=0.06), whereas HR was similar (92.3±4.9 vs. 93.9±3.9% of the peak of HR, p=0.10). [La]b was lower for handball than for IE (8.9±3.5 vs. 11.6±2.1mmoll−1, p=0.04). Time spent over 90% of V˙O2max was higher for handball than for IE (336.1±139.6s vs. 216.1±124.7s; p=0.03). The HR−V˙O2 relationship during GT was high (r2=0.96, p<0.001) but estimated V˙O2 from HR was lower to that measured (p=0.03) in handball, whereas there was no difference in IE. 4-a-side handball game can be used as a specific alternative to IE for enhancing aerobic fitness in handball players. Nevertheless, the accuracy of HR measures for estimating V˙O2 during handball is poor.