Rupture of the biceps tendon occurs predominantly in the middle-aged and elderly, being predisposed through bicipital tendinitis and rotator cuff lesions. Surgical repair may be an option for those requiring strength in supination. This study compared the initial fixation strength of keyhole tenodesis (n = 7) and interference screw fixation by use of cadaveric specimens. Two interference screws were evaluated (n = 7 × 2): the round-headed cannulated interference screw (RCI) and a bioresorbable screw (Sysorb). All specimens failed at the fixation site but one. This study found that overall there was a significant effect as a result of study group (keyhole vs Sysorb vs RCI, P = .034). The post hoc comparisons revealed that the keyhole was significantly stronger than the RCI screw ( P = .033) but not significantly different compared with the Sysorb screw ( P = .129). No significant difference was observed between the Sysorb and RCI screws ( P = .762). Interference screw fixation failed by tendon slippage at the screw-tendon-bone interface; keyhole fixation failed by tendon splitting and slippage out of the restraining keyhole. Keyhole tenodesis may permit earlier postoperative mobilization when compared with tenodesis by use of interference screw fixation.