The Healthy 4U-2 randomised controlled trial demonstrated that a physical activity (PA) telephone coaching intervention was effective for improving objectively-measured PA and health-related outcomes. The current study reports on an economic evaluation performed alongside the trial to determine whether this effective intervention is also cost-effective from a healthcare funder perspective. Participants (N = 120) were insufficiently physically active adults recruited from an ambulatory care clinic in a public hospital in regional Australia. The primary outcome was change in moderate-to-vigorous physical activity (MVPA) measured using accelerometers. Changes in quality-adjusted life-years (QALYs) were derived from the 12-Item Short Form Health Survey Questionnaire (SF-12). Incremental cost-effectiveness ratios (ICERs) were calculated for each outcome. Uncertainty of cost-effectiveness results were estimated using non-parametric bootstrapping techniques and sensitivity analyses. The mean intervention cost was $132 per person. The control group incurred higher overall costs compared to intervention ($2,465 vs. $1,743, respectively). Relative to control, the intervention resulted in incremental improvements in MVPA and QALYs and was deemed cost-effective. Probabilistic sensitivity analysis indicated that compared to control, the intervention would be cost-effective for improving MVPA and QALYs at very low willingness to pay thresholds. Sensitivity analyses indicated that results were robust to varied assumptions. This study shows that PA telephone coaching was a low-cost strategy for increasing MVPA and QALYs in insufficiently active ambulatory hospital patients. Findings of health benefits and overall cost-savings are uncommon and PA telephone coaching offers a potentially cost-effective investment to produce important public health outcomes.