• To examine compliance, clearance rates and cost-effectiveness of a novel approach to managing men following vasectomy based on the testing of sperm viability. • Between January 2003 and March 2005, 832 men undergoing vasectomy were followed prospectively for a minimum of 12 months. • Post-vasectomy semen analysis (PVSA) was carried out at 16 weeks with repeat at 20 weeks only if sperm were detected on initial PVSA i.e. a single clear PVSA on simple microscopy was deemed sufficient for declaring vasectomy successful. • In men with persistent non-motile sperm (PNMS) in the second specimen, comprehensive analysis of number and viability of sperm using a fluorescent probe was carried out on a fresh semen specimen taken in accordance with British Andrology Society (BAS) guidelines. • Overall compliance with the PVSA protocol was 81.3% (95% CI 78.5 to 83.8). No sperm were seen in 540 (78.8%) and 70 (10.3%) at the initial and 2(nd) PVSA respectively. • Persistent spermatozoa at 20 weeks were present in 66 (9.8%, 7.8 to 12.2) cases with 58 (8.6%, 6.7 to 11.0) having PNMS and 8 (1.2%, 0.6 to 2.3) having motile sperm. • Fluorescent viability testing in 53 of the 58 with PNMS showed viable sperm in 2 (3.8%, 1.0 to 12.8). The failure rate of vasectomy defined by PVSA (8 with motile sperm on 2(nd) PVSA and 2 with viable non-motile sperm on fluorescent testing) was 1.2% (0.7 to 2.2). • Average cost per vasectomy of PVSA using this protocol was £10.77 (US$ 16.67) compared with a minimum likely average cost using BAS guidelines of £18.10 (US$ 28). • Demonstrating absence of sperm on simple light microscopy in a single specimen of semen at 16 or 20 weeks post-vasectomy and reserving comprehensive testing of sperm viability for only the higher risk group with PNMS improves compliance and represents a cost-effective strategy for declaring surgical success. This reduces the costs of PVSA by least 40% compared with adherence with BAS guidelines without compromising success in determining outcome after vasectomy.